81_FR_2816 81 FR 2805 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins and Enhanced Biosafety Requirements

81 FR 2805 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins and Enhanced Biosafety Requirements

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Federal Register Volume 81, Issue 11 (January 19, 2016)

Page Range2805-2818
FR Document2016-00758

In accordance with the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Response Act), the Centers for Disease Control and Prevention (CDC) in the Department of Health and Human Services (HHS) has reviewed the list of biological agents and toxins that have the potential to pose a severe threat to public health and safety and proposes to amend and republish the list. Specifically, we are proposing to remove six biological agents; add provisions to address the inactivation of select agents; add specific provisions to the section of the regulations addressing biosafety; and clarify regulatory language concerning security, training, incident response, and records.

Federal Register, Volume 81 Issue 11 (Tuesday, January 19, 2016)
[Federal Register Volume 81, Number 11 (Tuesday, January 19, 2016)]
[Proposed Rules]
[Pages 2805-2818]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-00758]



[[Page 2805]]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Docket No. CDC-2015-0006]

42 CFR Part 73

RIN 0920-AA59


Possession, Use, and Transfer of Select Agents and Toxins; 
Biennial Review of the List of Select Agents and Toxins and Enhanced 
Biosafety Requirements

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Notice of Proposed Rulemaking (NPRM).

-----------------------------------------------------------------------

SUMMARY: In accordance with the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002 (the Bioterrorism Response Act), 
the Centers for Disease Control and Prevention (CDC) in the Department 
of Health and Human Services (HHS) has reviewed the list of biological 
agents and toxins that have the potential to pose a severe threat to 
public health and safety and proposes to amend and republish the list. 
Specifically, we are proposing to remove six biological agents; add 
provisions to address the inactivation of select agents; add specific 
provisions to the section of the regulations addressing biosafety; and 
clarify regulatory language concerning security, training, incident 
response, and records.

DATES: Submit written or electronic comments by March 21, 2016.

ADDRESSES: You may submit comments, identified by Docket No. CDC-2015-
0006 or RIN 0920-AA59 by any of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Mail: Division of Select Agents and Toxins, Centers for 
Disease Control and Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, 
Georgia 30329, Attn: Docket CDC-2015-0006.
    Instructions: All submissions received must include the agency name 
and docket number or Regulatory Information Number (RIN) for this 
rulemaking. All relevant comments received will be posted without 
change to http://regulations.gov, including any personal information 
provided. For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov.
    Comments will also be available for public inspection from Monday 
through Friday, except for legal holidays, from 9 a.m. to 5 p.m., 
Eastern Time, at 1600 Clifton Road NE., Atlanta, Georgia, 30329. Please 
call ahead to (404) 718-2000 and ask for a representative from the 
Division of Select Agents and Toxins to schedule your visit.

FOR FURTHER INFORMATION CONTACT: Dr. Dan Sosin, Acting Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, Georgia 30329. 
Telephone: (404) 718-2000.

SUPPLEMENTARY INFORMATION: 
    The NPRM is organized as follows:

I. Public Participation
II. Background
    A. Legal Authority
    B. Historical background to this rulemaking
III. Summary of Proposed Changes to 42 CFR part 73
    A. Definitions
    B. Proposed changes to the list of select agents
    C. Inactivation of a Select Agent
    D. Toxins
    E. Exemptions for select agents and toxins
    F. Registration
    G. Responsible Official
    H. Visitor Access to Select Agents and Toxins
    I. Security, Biosafety, and Incident Response Plans
    J. Training
    K. Records
IV. Alternatives Considered
V. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. The Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. EO 12988: Civil Justice Reform
    E. EO 13132: Federalism
    F. Plain Language Act of 2010
VI. References

I. Public Participation

    Interested persons or organizations are invited to participate in 
this rulemaking by submitting written views, recommendations, and data. 
Comments are invited on any topic related to this rulemaking.
    In addition, HHS/CDC invites comments specifically as to whether 
there are biological agents or toxins that should be added or removed 
from the HHS list of select agents and toxins based on the following 
criteria:
    (1) The effect on human health of exposure to the agent or toxin;
    (2) The degree of contagiousness of the agent or toxin and the 
methods by which the agent or toxin is transferred to humans;
    (3) The availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent any illness resulting from infection 
by the agent or exposure to the toxin; and
    (4) Any other criteria, including the needs of children and other 
vulnerable populations that the commenter considers appropriate.
    HHS/CDC also invites comments on the following questions:
    (1) Are there other methods that should be required to validate the 
rendering of a select agent non-viable or regulated nucleic acids that 
can produce infectious forms of any select agent virus non-infectious?
    (2) Should there be changes to the toxin permissible limits for 
excluded toxins?
    (3) Should Diacetoxyscirpenol (DAS) and T-2 be removed from the 
select toxin list because they do not have the potential to pose a 
severe threat to public health and safety?
    (4) Does seven calendar days provide a sufficient amount of time 
for the entity to destroy or transfer the select agents or toxins after 
identification?
    (5) Are there any specific biosafety measures that should be 
required to prevent laboratory acquired infections (LAIs) or accidental 
release of the select agents and toxins from an entity into the 
community?
    (6) What alternative regulatory requirement could be constructed 
such that a registered entity would know whether it had a theft or loss 
of a select agent or toxin without that registered entity first having 
``an accurate, current inventory for each select agent . . . held in 
long term storage''?
    Comments received, including attachments and other supporting 
materials, are part of the public record and subject to public 
disclosure. Do not include any information in your comment or 
supporting materials that you consider confidential or inappropriate 
for public disclosure. HHS/CDC will carefully consider all comments 
submitted in preparation of a final rule.

II. Background

A. Legal Authority

    HHS/CDC is promulgating this rule under the authority of sections 
201-204 and 221 of Title II of Public Law 107-188, 116 Stat 637 (42 
U.S.C. 262a).

B. Historical Background to This Rulemaking

    Subtitle A of the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002, (42 U.S.C. 262a), requires HHS 
to regulate the possession, use, and transfer of biological agents or 
toxins that have the potential to pose a severe threat to public health 
and safety (select agents and toxins). Subtitle B of the Public Health 
Security and Bioterrorism Preparedness and Response Act of 2002

[[Page 2806]]

(which may be cited as the Agricultural Bioterrorism Protection Act of 
2002), (7 U.S.C. 8401), requires the United States Department of 
Agriculture (USDA) to regulate the possession, use, and transfer of 
biological agents or toxins that have the potential to pose a severe 
threat to animal or plant health, or animal or plant products (select 
agents and toxins). Accordingly, HHS and USDA have promulgated 
regulations requiring individuals or entities that possess, use, or 
transfer select agents and toxins to register with the CDC or the 
Animal and Plant Health Inspection Service (APHIS). See 42 CFR part 73, 
7 CFR part 331, and 9 CFR part 121 (the select agent regulations). The 
Federal Select Agent Program (FSAP) is the collaboration of the CDC, 
Division of Select Agents and Toxins (DSAT) and the APHIS Agriculture 
Select Agent Services (AgSAS) to administer the select agent 
regulations in a manner that minimizes the administrative burden on 
persons subject to the select agent regulations. The FSAP administers 
the select agent regulations in close coordination with the Federal 
Bureau of Investigation's Criminal Justice Information Services 
Division (CJIS).
    The Bioterrorism Response Act also requires the HHS Secretary to 
establish by regulation a list of biological agents and toxins that 
have the potential to pose a severe threat to public health and safety. 
In determining whether to include an agent or toxin on the list, the 
HHS Secretary considers criteria such as the effect on human health of 
exposure to an agent or toxin; the degree of contagiousness of the 
agent and the methods by which the agent or toxin is transferred to 
humans; the availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent illnesses resulting from an agent or 
toxin; and the needs of children and other vulnerable populations. The 
current list of HHS select agents and toxins can be found at 42 CFR 
73.3 (HHS select agents and toxins) and 42 CFR 73.4 (Overlap select 
agents and toxins). The list of HHS and Overlap select agents and 
toxins is also available at: http://www.selectagents.gov/SelectAgentsandToxinsList.html.
    The HHS Secretary last republished the list of HHS select agents 
and toxins in the Federal Register on October 5, 2012 (77 FR 61084). 
The list of HHS select agents and toxins is divided into two sections. 
The select agents and toxins listed in section 73.3 (HHS select agents 
and toxins) are those regulated only by HHS under the authority of the 
Bioterrorism Response Act (42 U.S.C. 262a). The select agents and 
toxins listed in section 73.4 (Overlap select agents and toxins) are 
those regulated by HHS under the authority of the Bioterrorism Response 
Act and also regulated by the U.S. Department of Agriculture under the 
authority of the Agricultural Bioterrorism Protection Act of 2002 (7 
U.S.C. 8401).
    The Bioterrorism Response Act requires the HHS Secretary to review 
and republish the list of select agents and toxins on at least a 
biennial basis. Using government subject matter experts, HHS/CDC 
conducts the biennial review process in consultation with the HHS/CDC 
Intragovernmental Select Agents and Toxins Technical Advisory Committee 
(ISATTAC). The ISATTAC is comprised of Federal government employees 
from CDC, Biomedical Advanced Research and Development Authority 
(BARDA) within the Office of the Assistant Secretary for Preparedness 
and Response, the National Institutes of Health (NIH), the Food and 
Drug Administration (FDA), the Department of Homeland Security (DHS), 
the Department of Defense (DOD), the USDA/Animal and Plant Health 
Inspection Service (APHIS), USDA/Agricultural Research Service (ARS), 
and USDA Center for Veterinary Biologics (CVB). Based on the criteria 
outlined in the Bioterrorism Response Act, the ISATTAC considered the 
following criteria in their review of the HHS and Overlap lists of 
select agents and toxins: The degree of pathogenicity (ability of an 
organism to cause disease), communicability (ability to spread from 
infected to susceptible hosts), ease of dissemination, route of 
exposure, environmental stability, ease of production in the 
laboratory, ability to genetically manipulate or alter, long-term 
health effects, acute morbidity (illness), mortality, available 
treatment, status of host immunity, vulnerability of special 
populations, and the burden or impact on the health care system.
    On February 27, 2015, HHS/CDC published an advance notice of 
proposed rulemaking (80 FR 10656) in which we requested public comment 
on (1) whether there are biological agents or toxins that should be 
added or removed from the HHS list of select agents and toxins; and (2) 
whether HHS/CDC should remove the following six select agents from the 
HHS list of select agents and toxins: Coxiella burnetti, Rickettsia 
prowazekii, Bacillus anthracis Pasteur strain, Brucella abortus, 
Brucella melitensis, and Brucella suis.

III. Summary of Proposed Changes

    The following changes to the list of HHS select agents and toxins 
are proposed based on comments received to the advance notice of 
proposed rulemaking (80 FR 10656) referenced above, recommendations 
from the ISATTAC, information from the DHS Material Threat 
Determinations (DHS-MTD) of biological agents and toxins (https://www.medicalcountermeasures.gov/phemce/dhs.aspx), and the expertise of 
federal agencies and staff responsible for the oversight of the 
possession, use, and transfer of select agents and toxins. We are also 
proposing specific changes to the current regulations, as discussed 
below, addressing biosafety; clarifying regulatory language concerning 
security, training, incident response, and records; correcting an 
omission from the technical amendment (appeal process for exclusion); 
and revision of the select agent list with current taxonomic names.

A. Definitions

    We are proposing to add two new terms to section 73.1 (Definitions) 
of the regulations. We are proposing to define the term 
``Inactivation'' as ``a method to render a select agent non-viable but 
retain characteristic of interest for future use, or to render any 
nucleic acids that can produce infectious forms of any select agent 
virus non-infectious for future use.'' We are also proposing to define 
the term ``Kill curve'' as ``the results of a dose-response experiment 
where a select agent is subjected to increasing amounts of the 
inactivating treatment to determine the minimum conditions required to 
render it non-viable or to render any nucleic acids that can produce 
infectious forms of any select agent virus as non-infectious.'' The new 
definitions will help clarify proposed regulatory language in section 
73.12 (Biosafety).

B. Proposed Changes to the List of Select Agents

    On February 27, 2015, HHS/CDC published an advance notice of 
proposed rulemaking (ANPRM) (80 FR 10656) in which we requested public 
comment specifically on whether there are biological agents or toxins 
that should be added or removed from the HHS list of select agents and 
toxins.
    In that same docket, HHS/CDC also requested public comments as to 
whether biological agents specifically listed in the February 27, 2015 
ANPRM should be removed or remain on the list. The listed agents were 
Coxiella burnetti, Rickettsia prowazekii, Bacillus anthracis Pasteur 
strain, Brucella abortus, Brucella melitensis, and Brucella suis. We 
are now proposing that these agents be removed from the

[[Page 2807]]

HHS list of select agents based on the twenty-two comments received in 
response to the February 27, 2015 ANPRM, recommendations from the 
ISATTAC, and our review of current scientific data regarding these 
biological agents.
Coxiella burnetii (42 CFR 73.3)
    In response to the February 27, 2015 ANPRM, we received 11 comments 
concerning Coxiella burnetii. Only two commenters recommended that C. 
burnetii remain on the list because ``antibiotic treatment should not 
be considered for removing the agent.'' The other nine commenters 
argued that C. burnetii should not be included as a select agent based 
on the following assertions:
     Five commenters stated it is not easily transmitted from 
person to person.
     Three commenters referenced that even in the absence of 
antibiotic treatment, Q fever (the disease with acute and chronic 
stages caused by the bacteria C. burnetii) is generally a self-limited 
flu-like illness with low mortality (Ref. 1).
     All commenters acknowledged that most infections are 
inapparent and most seropositive individuals cannot remember an 
infection consistent with Q fever.
     Six commenters agreed that Coxiella is susceptible to a 
number of readily available antibiotics. Preferred treatments include 
tetracycline or doxycycline. Quinolones have also been used 
successfully and Co-trimoxazole is recommended in specific situations 
such as pregnancy.
    The ISATTAC recommended the removal of C. burnetii from the HHS 
list of select agents and toxins because:
     It has a low mortality rate with antibiotic treatment and 
most seropositive individuals cannot remember an infection consistent 
with Q fever (Ref. 2); and
     A whole-cell killed vaccine (Q-Vax) with nearly 100% 
efficacy is licensed in Australia and has been used to vaccinate U.S. 
researchers whom were at risk (Ref. 3).
    We are now proposing to remove C. burnetii from the HHS list of 
select agents (42 CFR 73.3). As discussed above, our proposal is 
supported by comments we received in response to the February 27, 2015 
ANPRM and the recommendations of the ISATTAC. Both the commenters and 
the ISATTAC supported their recommendations with the scientific 
references noted above. We further conclude that, based on recent 
information provided by DHS-MTD, C. burnetii does not pose a severe 
threat to public health and safety. We are, however, still seeking 
comment from those who may believe that C. burnetii remains a severe 
threat to public health and safety and accordingly should be retained 
as a HHS select agent.
Rickettsia prowazekii (42 CFR 73.3)
    In response to the February 27, 2015 ANPRM, we received eight 
comments concerning Rickettsia prowazekii. Only one commenter 
recommended to retain Rickettsia prowazekii because ``antibiotic 
treatment should not be considered for removing the agent.'' The other 
seven commenters supported removal based on the following reasons:
     The risk of mass casualties is low because R. prowazekii 
can be treated with a single dose of doxycycline when symptoms are 
present;
     Transmissibility from person to person is low due to the 
fact that R. prowazekii is usually transmitted via blood, although it 
can be spread through inhalation of louse feces;
     The agent has poor environmental stability; and
     The difficulty in growing and purifying substantial 
quantities of these agents in vitro.
    The ISATTAC recommended the removal of R. prowazekii from the HHS 
list of select agents and toxins because:
     It is treatable with available antibiotics (Ref. 4 and 5);
     The risk of mass casualties is low because R. prowazekii 
can be treated with a single dose of doxycycline when symptoms are 
present (Ref. 4 and 5); and
     Transmissibility from person to person is low due to the 
fact that R. prowazekii is usually transmitted via blood, although it 
can be spread through inhalation of louse feces (Ref. 5).
    We are now proposing to remove R. prowazekii from the HHS list of 
select agents (42 CFR 73.3). As discussed above, our proposal is 
supported by the comments we received in response to the February 27, 
2015 ANPRM and the recommendations of the ISATTAC. Both the commenters 
and the ISATTAC supported their recommendations with the scientific 
references noted above. We further conclude that, based on recent 
information provided by DHS-MTD, R. prowazekii does not pose a severe 
threat to public health and safety. We are, however, still seeking 
comment from those who may believe that R. prowazekii remains a severe 
threat to public health and safety and accordingly should be retained 
as a HHS select agent.
Bacillus anthracis Pasteur Strain (42 CFR 73.4)
    We received six comments to the February 27, 2015 ANPRM with all 
commenters agreeing that Bacillus anthracis Pasteur strain should not 
be included as a select agent based on B. anthracis Pasteur strain 
lacks the plasmid that encodes the toxin genes causing disease. The B. 
anthracis Sterne strain, which lacks the plasmid that encodes for the 
capsule, was excluded from the requirements of the regulations 
effective on February 27, 2003.
    The ISATTAC recommended the removal of B. anthracis Pasteur strain 
from the overlap list of select agents and toxins because:
     B. anthracis Pasteur strain lacks the plasmid that encodes 
the toxin genes causing disease (Ref. 6);
     B. anthracis Sterne strain, which lacks the plasmid that 
encodes for the capsule, was excluded from the requirements of the 
regulations effective on February 27, 2003 (Ref. 7-8); and
     Historically, the B. anthracis Pasteur strain has been 
retained as a select agent to allow for continued oversight of 
laboratories in which the accidental (or intentional) combination of 
this strain with the Sterne strain could occur to produce de novo the 
wild type phenotype B. anthracis. However, a recent study indicates 
that bacterial transformation of B. subtilis with plasmid DNA is 
inefficient; indicating that transformation with plasmid pXO1 into 
closely related bacteria such as the Bacillus anthracis Pasteur strain 
would also be inefficient (Ref. 9).
    We agreed with the commenters and ISATTAC. We propose to remove B. 
anthracis Pasteur strain because the transformation of a virulence 
plasmid from one Bacillus strain to another is difficult.
Brucella abortus, B. melitensis, and B. suis (42 CFR 73.4)
    Responses were received from 16 commenters to the February 27, 2015 
ANPRM, that addressed the retention of the three Brucella species (B. 
abortus, B. melitensis, and B. suis) currently on the overlap select 
agent list. Only two commenters recommended to retain these species 
because ``antibiotic treatment should not be considered for removing 
the agent.'' The other 14 commenters supported removal based on the 
rationale provided in the ANPRM.
    The ISATTAC recommended the removal of B. abortus, B. melitensis, 
and B. suis from the overlap list of select agents and toxins because:
     B. abortus has a low human mortality rate (Ref. 10);

[[Page 2808]]

     B. abortus, B. melitensis, and B. suis are treatable with 
antibiotics (Ref. 10); and
     Human-to-human transmission is extremely rare, and 
wildlife carriers in the United States often come into contact with 
humans without significant transmission (Ref. 10).
    We agreed with the commenters and ISATTAC. We propose to remove B. 
abortus, B. melitensis, and B. suis because although Brucella has a low 
infectious dose, it is treated, mortality is low, efficacy of treatment 
is good for all three Brucella strains.

C. Inactivation of a Select Agent

    We are proposing to add specific requirements to the biosafety 
section of the regulations (42 CFR 73.12) to address the requirements 
for rendering a select agent or an nucleic acids that can produce 
infectious forms of any select agent virus ``non-viable.''
    Sections 73.3 (HHS select agents and toxins) and 73.4 (Overlap 
select agents and toxins) both provide that a ``non-viable'' select 
agent is excluded from the requirements of the select agent 
regulations. We are proposing that for an agent to be ``non-viable,'' 
or to render a nucleic acids that can produce infectious forms of any 
select agent virus non-infectious for future use, an entity must use a 
validated method. A validated method means that the method must be 
scientifically sound such that method will produce consistent results 
each time the method is used. As outlined in our guidance for ``Non-
viable Select Agents and Nonfunctional Select Toxins and Rendering 
Samples Free of Select Agents and Toxins'' (http://www.selectagents.gov/guidance-nonviable.html), an inactivation 
procedure may include (1) use of the exact conditions of an accepted 
method that has been validated, such as autoclaving, (2) a published 
method with adherence to the exact published conditions, or (3) for in-
house methods, validation testing should include the specific 
conditions used and appropriate controls.
    As part of the inactivation procedure, an entity would be required 
to develop a site specific kill curve to identify conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve would be required to 
be developed for each strain that undergoes the inactivation procedure. 
A new kill curve would also be required to be created upon any change 
in procedure or inactivation equipment. In addition, a validated 
sterility testing protocol to ensure that the inactivation method has 
rendered a select agent non-viable or regulated nucleic acids that can 
produce infectious forms of any select agent virus non-infectious would 
be required to be conducted.9ij
    We are also proposing that written records be kept for a select 
agent or extracts that have been subjected to a procedure to render 
them non-viable or regulated nucleic acids that can produce infectious 
forms of any select agent virus that have been subjected to a procedure 
to render them non-infectious.
    We are also soliciting ideas as to whether there are other methods 
that should be required to validate the rendering of a select agent 
non-viable or regulated nucleic acids that can produce infectious forms 
of any select agent virus non-infectious.

D. Toxins

Due Diligence
    Section 73.3(d)(3) of the select agent regulations (42 CFR 
73.(d)(3))specifies the select toxin amounts under the control of a 
principal investigator, treating physician or veterinarian, or 
commercial manufacturer or distributor that are excluded from the 
requirements of the select agent regulations. However, this exclusion 
applies to the transfer of select toxins ``only after the transferor 
uses due diligence and documents that the recipient has a legitimate 
need . . . to handle or use such toxins'' (42 CFR 73.3(d)(3)(i)). This 
provision was added to the select agent regulations to address the 
concern that someone might be able to covertly stockpile toxins by 
receiving multiple orders below the excluded amount. The toxin ``due 
diligence'' provision requires a person transferring toxins in amounts 
which would otherwise be excluded from the provisions to: (1) Use due 
diligence to assure that the recipient has a legitimate need to handle 
or use such toxins; and (2) report to the FSAP if they detect a known 
or suspected violation of Federal law or become aware of suspicious 
activity related to the toxin.
    ``Due diligence'' is generally understood to be such a measure of 
prudence, activity, or assiduity, as is properly to be expected from, 
and ordinarily exercised by, a reasonable and prudent person under the 
particular circumstances; not measured by any absolute standard, but 
depending on the relative facts of the specific case.
    We are proposing to add a more specific documentation requirement 
to the toxin exclusion provision to require the transferor to document 
the identity of the recipient and the legitimate need (i.e., 
prophylactic, protective, bona fide research, or other peaceful 
purpose) claimed by the transferee. Information required to be 
documented would also include the name of the toxin and the total 
amount transferred. Identity information of the person requesting and 
using the toxins would include the individual's name, institution name, 
address, telephone number, and email address.
Toxin Permissible Limits
    In conjunction with this biennial review, the FSAP solicited input 
from biological toxin subject matter experts to review the listed 
exclusion limits for select toxins in the HHS select agent regulations. 
To assess the amount necessary to weaponize a biological toxin, DHS 
developed toxin parameters and attack scenarios for potential 
inhalation and ingestion exposures to select toxins. DHS used the 
formulas described below to estimate ingestion scenarios while 
employing the ``NIST CONTAM Multizone Modeling'' software (http://www.bfrl.nist.gov/IAQanalysis/) for inhalation scenarios. To estimate 
the amount of toxin for each scenario, DHS analyzed a range of release 
sizes (in mg) for each biological toxin in order to estimate the number 
of people that would be exposed to LD-50 (lethal dose, 50% or median 
lethal dose, the amount of the substance required (usually per body 
weight) to kill 50% of the test population); or TD-50 (the median toxic 
dose of a toxin is the dose at which toxicity occurs in 50% of cases) 
levels of each toxin amount by ingestion of milk (using published TD-50 
or LD-50) and/or indoor inhalation (using published LD-50). The 
inhalation models analyzed toxin releases in three different indoor 
public facilities that experience heavy commuter volume (population 
details for these facilities are given in Table 1). One hundred 
scenarios were generated for each facility using 1-10[micro]m particle 
sizes. The models used 10 random locations within each facility 
(potential release locations and population evenly spaced throughout 
occupied area) at 10 random times. The inhalation models assumed:
     No immediate symptoms, so no changes in population 
movement due to attack
     Respiration rate 10L/min
     All people assumed to have the same mass = 70 kg (e.g., 
did not account for lower doses required for children)

[[Page 2809]]



                           Table 1--Summary of Facility Population and Residence Times
----------------------------------------------------------------------------------------------------------------
                                                                                                    Simulation
                                                                    2008 Annual     Simulation       transient
                            Facility                                 passenger       transient        average
                                                                      traffic         hourly      residence time
                                                                     (people)       population       (minutes)
----------------------------------------------------------------------------------------------------------------
High throughput transportation facilities.......................     255,500,000          43,750              10
High throughput transportation facilities.......................     219,000,000          37,500              15
High throughput transportation facilities.......................      64,300,000          11,005              60
----------------------------------------------------------------------------------------------------------------

    The ingestion models investigated biological toxins introduced into 
a fluid (e.g., milk) that was purchased and consumed by consumers over 
a two day period. Production details and specifics of how the toxins 
were introduced were not considered. In particular, the largest 
scenarios involve contaminating greater than ten million servings, 
which was determined to be implausible in practice. The ingestion 
models made the following assumptions:
     Milk containing specified quantity of active toxin (1 mg 
to 1 kg) reaches store shelves.
     Milk is consumed over six days at a uniform rate.
     Contaminated milk is consumed daily until supply is 
depleted or a health advisory is issued.
     Milk contamination discovered and health advisory issued a 
minimum of one day, and a maximum of >1 week post attack (at which 
point all contaminated milk has been consumed).
     For toxins other than saxitoxin and tetrodotoxin, the 
attacker chooses a toxin concentration such that a person in the 45+ 
years old age group will consume 1 LD-50 (or TD-50) over 6 day 
consumption period.
     Since saxitoxin and tetrodotoxin are largely excreted in 
approximately one day after consumption, the attacker chooses a 
saxitoxin or tetrodotoxin concentration such that a person in the 45+ 
years old age group will consume 1 LD-50 (or TD-50) over a one day 
consumption period.
     Total volume of milk contaminated equals the number of 
grams of toxin available divided by the toxin concentration (i.e., 
total volume of milk contaminated depends on the mass of toxin assumed 
to be available (which varies from 1 mg to 1 kg) and the toxin 
ingestion LD-50 (or TD-50)).
     If the toxin ingestion LD-50 (or TD-50) is given by a 
range, the geometric mean of this range is used.
     Range of total volumes of milk contaminated is less than 1 
L to approximately 10\8\ L.
     The amount of milk contaminated is assumed to depend on 
how much toxin the attacker has available (i.e., the total volume of 
milk contaminated equals the number of grams of toxin available divided 
by the toxin concentration). For example, for a 1 g attack, with a 
toxin that has an LD-50 of 1mg/kg, the volume of milk contaminated 
would be 1000 mg/(0.056 mg/mL*1000 mL/L) = 18 L of milk.
     For small attack sizes, it is assumed the attacker would 
target appropriately-sized small holding tanks or containers, while for 
large attack sizes, the attacker would target large holding tanks or 
silos.
     If the toxin is degraded due to pasteurization or storage, 
the amount of toxin introduced pre-processing would have to be 
correspondingly larger than these masses.
Proposed Increase of Regulatory Exclusion Limits
    Based on the data generated by the models described above, we are 
proposing the following exclusion limits based on the amounts estimated 
to expose less than 10 people by inhalation or less than 100 people by 
ingestion to the LD-50 or TD-50 levels of toxin:
     Increase the regulatory exclusion limit of Botulinum 
neurotoxin (BoNT) from 0.5 mg to 1 mg;
     Increase the regulatory exclusion limit of Staphylococcal 
enterotoxins from 5 mg to 100 mg;
     Increase the regulatory exclusion limit of saxitoxin from 
100 mg to 500 mg;
     Increase the regulatory exclusion limit of tetrodotoxin 
from 100 mg to 500 mg;
     Increase the regulatory exclusion limit of abrin from 100 
mg to 1,000 mg;
     Increase the regulatory exclusion limit of ricin from 100 
mg to 1,000 mg; and
     Increase the regulatory exclusion limit of DAS from 1,000 
mg to 10,000 mg.
     Increase the regulatory exclusion limit of T-2 from 1,000 
mg to 10,000 mg.
    We are, however, still seeking comment from those who may believe 
that we should retain the current exclusion limits. In addition, we are 
interested in receiving comments from the public on whether DAS and T-2 
have the potential to pose a severe threat to public health and safety 
or whether these two toxins should be removed from the select toxin 
list given the high exclusion limit for DAS and T-2.
Proposed Removal of Select Toxins
Short, Paralytic Alpha-Conotoxins
    We are proposing short, paralytic alpha-conotoxins containing the 
following amino acid sequence 
(X1CCX2PACGX3X4X5
X6CX7) be removed as a select toxin for the 
following reasons:
     The DHS model reported LD-50 value for inhalation delivery 
of alpha-conotoxin is 20 [micro]g/kg, which is a low toxicity compared 
to other select toxins;
     A regulatory exclusion limit of 10,000 mg would require 
the depletion of the cone snail population to achieve this quantity.
    Therefore, based on the low toxicity of short, paralytic alpha-
conotoxins and the high dosage required for inhalation exposure, we are 
proposing that the alpha-conotoxin be removed from the select toxin 
list (Ref. 32).
Toxins: Exclusion of Original Food Samples and Clinical Samples
    Original food samples and clinical samples are those specimens that 
are submitted to laboratories for diagnosis or verification purposes to 
identify or verify a biological agent or toxin. For example, an 
original food sample could be a container of potato salad or juice. An 
original clinical sample could be serum or stool from a patient. 
Laboratories that test food sample and clinical samples for the 
presence of toxins generally do not know the level of toxin in a sample 
and do not extract and purify a toxin as part of their studies. 
Therefore, we are proposing to exclude the original food sample or 
clinical sample identified to contain an HHS select toxin to be 
consistent with the rationale for the current exclusion for animals 
exposed to toxins (42 CFR 73.3(d)(4)). The proposed exclusion is based 
upon input from biological toxin subject matter experts and our 
determination that quantifying the

[[Page 2810]]

amount of toxin in these samples is problematic because (1) the amount 
of toxin is highly variable, which would require large amounts of food 
and clinical samples to quantify or purify, (2) laboratory procedures 
to extract toxin from samples are inefficient with most extractions 
producing low yields; (3) the resources that would be required to 
quantify toxins in clinical samples and food samples make sample 
quantification prohibitively expensive; and (4) procedures in these 
laboratories, based on the requirements of their public health mission, 
are designed only for toxin detection and not for purification and 
quantification. Therefore, we are interested in comments regarding our 
rationale that the original food sample or clinical sample identified 
to contain an HHS select toxin should be excluded from the select agent 
regulation.
Exclusion of Toxin Produced as a Byproduct
    Laboratories that are only registered for BoNT-producing species of 
Clostridium do not normally have a need to account for BoNT produced 
during the culturing of Clostridium since studying the toxin is not 
part of their work objective. Therefore, we propose to exclude toxins 
that are produced only as a byproduct to a study of the toxin producing 
host organism so long as the toxin has not been intentionally 
collected, purified, or otherwise extracted, and the material 
containing the toxin is inactivated and properly disposed of within 30 
days of the initiation of the culture. The 30 day disposal time was 
recommended by biological toxin subject matter experts based on the 
time it would take to grow the organism and perform the extraction 
process. This exclusion allows laboratories whose purpose does not 
include purification of the toxin to more effectively conduct outbreak 
investigations, food studies, and molecular characterization of agents 
which produce toxin. In the case of BoNT, these laboratories would 
still be regulated for the BoNT-producing species of Clostridium and in 
the case of all other HHS select toxins the laboratories would be 
regulated if they wished to keep the material containing toxins for 
longer than 30 days from the initiation of culture of the toxin 
producing host organism. If at any time an entity manipulated the 
material that contains the select toxin, such as intentional 
collection, purification or extraction of the toxin from culture 
supernatant, such activities would void this exemption, and the entity 
would be required to be registered for the select toxin and meet all 
applicable select agent and toxin regulatory requirements.

E. Exemptions for Select Agents and Toxins

Informing Specimen Provider
    Since a registered or certified reference laboratory typically 
confirms the identification of a select agent or toxin for public 
health and agriculture, clinical and diagnostic laboratories, we are 
proposing to require the registered or certified reference laboratory 
inform the specimen provider of the identification. This will ensure 
that the reference laboratory notifies the specimen provider of the 
identification of the select agent or toxin so that the specimen 
provider is aware that they are in possession of the agent or toxin and 
must meet the requirements outlined in 42 CFR 73.5, 73.6.
Identification of Toxin
    Once a clinical or diagnostic laboratory has identified a select 
toxin-positive specimen, an APHIS/CDC Form 4 (Report of the 
Identification of a Select Agent or Toxin) must be submitted to the 
FSAP. The select agent regulations currently require the laboratory to 
transfer or destroy the material within seven days of identification 
(42 CFR 73.5(a), 73.6(a)) because we determined through input from 
technical experts that the seven calendar days provides a sufficient 
amount of time for the entity to destroy or transfer the select agents 
or toxins after identification. In the past, we have received comments 
that argued that the seven day requirement for transferring or 
destroying select agents or toxins used for diagnosis or testing is too 
short a time limit. Therefore, we are seeking comments to determine if 
seven calendar days provides a sufficient amount of time for the entity 
to destroy or transfer the select agents or toxins after 
identification.
    In addition, we are seeking comments to extend the exemption time 
period to 30 days for BoNT and Staphylococcal enterotoxin (Subtypes A-
E) to allow clinical and diagnostic laboratories sufficient time to 
complete their investigations without having to transfer or destroy the 
sample. Laboratories would still be required to report the 
identification of BoNT immediately and Staphylococcal enterotoxin 
(Subtypes A-E) within seven days. We are proposing to amend the 
language in 42 CFR 73.5(a), and 42 CFR 73.6(a)to read: ``Unless 
directed otherwise by the HHS Secretary, within seven calendar days 
after identification of the select agent and toxin (except for 
Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E)), 
or within thirty calendar days after identification of Botulinum 
neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E), the select 
agent or toxin is transferred in accordance with Sec.  73.16 or 
destroyed on-site by a recognized sterilization or inactivation 
process,''
Patient Care
    To clarify how the select agent regulations apply to activities 
associated with the diagnosis and care for individuals infected with a 
select agent or exposure to a select toxin, we are proposing to add 
provisions that HHS/CDC will not regulate material containing a select 
agent or toxin when it is in a patient care setting and is not being 
otherwise collected, tested or retained for non-patient care purposes. 
However, once delivery of patient care for an illness associated with a 
select agent or toxin has concluded these specimens would become 
subject to the regulatory requirements. An entity unable to meet all of 
the regulatory requirements necessary to retain the material will then 
have the option of transferring the material containing the select 
agent or toxin in accord with the select agent regulations or 
destroying the materials within seven calendar days of the conclusion 
of patient care.
    We also are proposing to clarify that FSAP does not regulate waste 
generated during the delivery of patient care.

F. Registration

    We are codifying in regulations the current FSAP policy that an 
entity is required to meet all of the regulatory requirements for those 
select agents and toxins listed on the entity's registration regardless 
of whether the select agent or toxin is in the actual possession of the 
entity; and without regard to the actual amounts of toxins in the 
possession of the entity.

G. Responsible Official (RO)

    Section 73.9(a)(6) of the select agent regulations currently states 
that the Responsible Official must ensure that an annual inspection is 
conducted for each laboratory where select agents and toxins are stored 
or used. This requirement also provides that the results of each 
inspection must be documented, and any deficiencies identified during 
an inspection must be corrected. We are adding a requirement that the 
Responsible Official must also document the corrective actions taken by 
the entity to address any identified deficiencies.

[[Page 2811]]

HHS or USDA Office of the Inspector General Hotline
    In response to a recommendation in the December 2014 Federal 
Experts Security Advisory Panel report, we are adding a requirement 
that the Responsible Official must ensure that individuals are provided 
the contact information of the HHS or USDA Office of Inspector General 
Hotline so that individuals are able to anonymously report a safety or 
security concern related to select agents and toxins. In its December 
2014 report, the Federal Experts Security Advisory Panel recommended 
adding a specific requirement to include how individuals are informed 
so that they can access the HHS or USDA Office of Inspector General 
Hotline to anonymously report a safety or security concern.

H. Visitor Access to Select Agents and Toxins

    Section 73.10(e) of the select agent regulations currently provides 
that a person with a valid approval from the HHS Secretary or APHIS 
Administrator to have access to select agents and toxins may request, 
through his or her Responsible Official, that the HHS Secretary or 
APHIS Administrator provide their approved access status to another 
registered individual or entity for a specified period of time. This 
allows a scientist registered to work with a select agent at a 
registered entity to work with the select agent at another registered 
entity. To ensure that the Responsible Official of the entity hosting 
the visitor is aware if a visiting individual loses approval for access 
to select agents and toxins, we are proposing to add a requirement that 
the Responsible Official at the home entity must immediately notify the 
Responsible Official of the visiting entity if the person's access to 
select agents or toxins has been terminated.

I. Security, Biosafety, and Incident Response Plans

    The select agent regulations require a registered entity to develop 
and implement a number of plans in order to ensure the safety and 
security of the select agents they handle. These are:
     A security plan that provides for measures sufficient to 
safeguard the select agent or toxin against unauthorized access, theft, 
loss, or release (42 CFR 73.11);
     A biosafety plan that provides for measures sufficient to 
contain the select agent or toxin (e.g., physical structure and 
features of the entity, and operational and procedural safeguards) (42 
CFR 73.12); and
     An incident response plan that provides for measures that 
the registered entity will implement in the event of theft, loss, or 
release of a select agent or toxin; inventory discrepancies; security 
breaches (including information systems); severe weather and other 
natural disasters; workplace violence; bomb threats and suspicious 
packages; and emergencies such as fire, gas leak, explosion, power 
outage, etc. The response procedures must account for hazards 
associated with the select agent or toxin and appropriate actions to 
contain such agent or toxin. (42 CFR 73.14)
    Drills or exercises must be conducted at least annually to test and 
evaluate the effectiveness of the plans. The plans must be reviewed and 
revised, as necessary, after any drill or exercise and after any 
incident. We are proposing to require that these drills or exercises be 
documented to include how the drill or exercise tested and evaluated 
the plan, any problems identified and corrective actions that were 
taken, and the names of the individuals who participated in the drill 
or exercise. This will provide a more thorough accounting of required 
activities via testing and entity-directed improvements.
    Similar to the existing requirement for the security plan, we are 
also proposing to add a requirement that the biosafety and incident 
response plans be submitted for initial registration, renewal of 
registration, or when requested by FSAP.
Biosafety
    We are proposing to amend the regulatory language in section 73.12 
to update the name change of the National Institutes of Health (NIH) 
Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid 
Molecules (Ref. 31).
    Prior to the publication of the 5th edition of CDC/NIH Biosafety in 
Microbiological and Biomedical Laboratories (Ref. 3), the Occupational 
Safety and Health Administration (OSHA) regulations in 29 CFR 1910.1200 
and 1910.1450 provided specific requirements for handling hazardous 
chemicals in the laboratories. This regulation also provided 
recommendations for safely working with chemical including toxins and 
gave non-mandatory recommendations for prudent practices in 
laboratories handling chemical hazards. As such, we included this 
reference for entities to consider when developing biosafety plans for 
those facilities working with toxins. Since the current edition of the 
CDC/NIH Biosafety in Microbiological and Biomedical Laboratories 
Appendix I provides guidelines for work with toxins of biological 
origin, we have removed the reference to the OSHA regulations in 29 CFR 
1910.1200 and 1910.1450. It should be noted that regulated entities 
must still meet the OSHA regulatory requirements where applicable.
    In addition, we want to ensure that laboratory personnel that are 
working with select agents and toxins are aware of the risks associated 
with these agents. As such, we are proposing to add a requirement that 
a laboratory-specific biosafety manual must be accessible to 
individuals. This is consistent with guidance provided by the CDC/NIH 
publication, Biosafety in Microbiological and Biomedical Laboratories. 
This requirement is proposed to foster an enhanced culture of 
responsibility by ensuring that appropriate biosafety resources are 
available to all staff with access to select agents and toxins within a 
select agent laboratory.
    The current regulations require that the biosafety plan be written 
using performance standards. In the aftermath of recent biosafety 
incidents involving select agents, we are proposing that the biosafety 
plan should be designed according to a site-specific risk assessment in 
accordance with the risk of a select agent, given its intended use by 
adding specific provisions to the biosafety section that would require 
a written risk assessment for each registered select agent or toxin; 
written safety procedures to protect entity personnel, the public, and 
the environment from exposure to the select agent or toxin; written 
decontamination procedures; and written waste management procedures.
    The FSAP would also like to solicit ideas regarding any specific 
biosafety measures that should be required to prevent LAIs or 
accidental or intentional release of the select agents and toxins from 
an entity into the community.
Security
    We are proposing to amend the requirement that the security plan 
contain a description of how the entity authorizes the means of entry 
into areas where select agents or toxins are stored or used, to include 
a requirement that the security plan must include a description of 
centralized access control management systems (e.g., keycards) and/or 
key management (mechanical keys).
    Paragraphs (d)(7)(i) through (d)(7)(v) of section 11 of the select 
agent regulations encompass a list of events that individuals with 
access approval from the APHIS Administrator or the

[[Page 2812]]

HHS Secretary must immediately report to the Responsible Official. We 
are proposing to add a new requirement that the Responsible Official 
must be notified of any loss of computer, hard drive, or other data 
storage device containing information that could be used to gain access 
to select agents or toxins. We believe that such notification will 
facilitate notification of the Federal Bureau of Investigation if 
deemed necessary by the Responsible Official as the loss of such 
equipment may be criminal in nature.

J. Training

    We are proposing to amend section 15 of the select agent 
regulations which concerns the provision of training for staff and 
visitors who work in or visit areas where select agents or toxins are 
handled or stored. Since individuals need to understand hazards 
associated with the select agents and toxins that they will be working 
with in the laboratory or are in the area they will be visiting, we are 
proposing to require that all individuals who have received approval to 
have access to select agents and toxins have training that address the 
particular needs of the individual and the risks posed by the select 
agent or toxin regardless of whether they have access to the select 
agents or toxins. The training would have to be completed within 12 
months of that individual's anniversary of receiving access approval or 
prior to his or her entry into an area where any select agents and 
toxins are used or stored, whichever occurs first. This change is 
necessary in order to codify our policy regarding which individuals at 
registered entities are required to receive training.
    We are also proposing to add a new paragraph (e) to section 15, 
which would require the entity's Responsible Official to provide 
contact information for the USDA or HHS Office of the Inspector General 
Hotline. Details of the proposed addition may be found under the 
heading ``Responsible Official.''

K. Records

    Based on inspections of registered entities, we observed that 
entities are maintaining records of the destruction of select agents 
even though section 73.17 of the select agent regulations currently 
does not include a requirement for documenting when a select agent is 
destroyed. To ensure the proper tracking of a select agent from 
acquisition to destruction and to incorporate into the regulations what 
entities are currently doing, we are proposing to add the requirement 
for records to be created and maintained for the destruction of a 
select agent held in long-term storage to include the quantity (i.e., 
number of vials) of select agent destroyed, the date of such action, 
and by whom.
    Section 73.17 of the select agent regulations currently states that 
records and databases need to be accurate. To ensure that handwritten 
records are accurate, we are proposing to clarify that hand-written 
record must be legible (i.e., capable of being read).
    We are proposing to expand the scope of records required to be 
maintained to include any records that contain information related to 
the requirements of the regulations. Such records may include, but 
would not limited to, biocontainment certifications, laboratory 
notebooks, institutional biosafety and/or animal use committee minutes 
and approved protocols, and records associated with occupational health 
and suitability programs. We propose revision to the regulations will 
enhance the ability of FSAP to evaluate biosafety, security, and 
incident response programs and includes any record created under 
sections 73.5, 73.7, 73.9, 73.11, 73.12, 73.14, 73.15, 73.16, 73.17, 
and 73.19 of the select agent regulations.
Records for Long-term Storage
    The FSAP continues to receive comments that are critical of that 
portion of the select agent regulations that require a registered 
entity to maintain ``an accurate, current inventory for each select 
agent . . . held in long term storage.'' The comments typically focus 
on the belief that a container based inventory requirement is not 
useful to track inventory of biological agents of which small amounts 
of samples from the container could be stolen without detection and 
used to grow larger quantities. In the Public Health Security and 
Bioterrorism Preparedness and Response Act of 2002, Congress requires 
the Secretaries of Health and Human Services and Agriculture to include 
in the select agent regulations a requirement for ``the prompt 
notification of the Secretary, and appropriate Federal, State, and 
local law enforcement agencies, of the theft or loss of listed agents 
and toxins.'' HHS/CDC is soliciting ideas on any alternative regulatory 
requirement that could be constructed such that a registered entity 
would know whether it had a theft or loss of a select agent or toxin 
without that registered entity first having ``an accurate, current 
inventory for each select agent . . . held in long term storage.''

V. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    Under Executive Order 12866 (EO 12866), Regulatory Planning and 
Review (58 FR 51735, October 4, 1993) HHS/CDC is required to determine 
whether this regulatory action would be ``significant'' and therefore 
subject to review by the Office of Management and Budget (OMB) and the 
requirements of the Executive Orders. This order defines ``significant 
regulatory action'' as any regulatory action that is likely to result 
in a rule that may:
     Have an annual effect on the economy of $100 million or 
more or adversely affect in a material way the economy, a sector of the 
economy, productivity, competition, jobs, the environment, public 
health or safety, or state, local, or tribal governments or 
communities;
     Create a serious inconsistency or otherwise interfere with 
an action taken or planned by another agency;
     Materially alter the budgetary impact of entitlements, 
grants, user fees, or loan programs or the rights and obligations of 
recipients; or,
     Raise novel legal or policy issues arising out of legal 
mandates, the President's priorities, or the principles set forth in EO 
12866.
    Executive Order 13563 (EO 13563), Improving Regulation and 
Regulatory Review, (76 FR 3821, January 21, 2011), updates some of the 
provisions of EO 12866 in order to promote more streamlined regulatory 
actions. This EO charges, in part, that, while protecting ``public 
health, welfare, safety, and our environment'' that regulations must 
also ``promote predictability and reduce uncertainty'' in order to 
promote economic growth. Further, regulations must be written in plain 
language and be easy to understand.
    HHS/CDC has determined that this NPRM is a significant regulatory 
action as defined in EO 12866. However, the Office of Management and 
Budget has waived their review of the document.

B. The Regulatory Flexibility Act (RFA), as Amended by the Small 
Business Regulatory Enforcement Fairness Act (SBREFA)

    We have examined the impacts of the proposed rule under the 
Regulatory Flexibility Act (5 U.S.C. 601-612). Unless we certify that 
the proposed rule is not expected to have a significant economic impact 
on a substantial number of small entities, the Regulatory Flexibility 
Act (RFA), as amended by the Small Business Regulatory Enforcement 
Fairness Act (SBREFA), requires agencies to analyze regulatory

[[Page 2813]]

options that would minimize any significant economic impact of a rule 
on small entities. We certify that this proposed rule will not have a 
significant economic impact on a substantial number of small entities 
within the meaning of the RFA.
    This regulatory action is not a major rule as defined by Sec. 804 
of the Small Business Regulatory Enforcement Fairness Act of 1996. This 
proposed rule will not result in an annual effect on the economy of 
$100,000,000 or more; a major increase in cost or prices; or 
significant adverse effects on competition, employment, investment, 
productivity, innovation, or on the ability of United States-based 
companies to compete with foreign-based companies in domestic and 
export markets.

C. Paperwork Reduction Act of 1995

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), HHS/CDC has determined that the 
Paperwork Reduction Act does apply to information collection and 
recordkeeping requirements included in this rule. We note that the 
information collection and recordkeeping requirements are already 
approved by the Office of Management and Budget (OMB) under OMB Control 
Number 0920-0576.

D. EO 12988: Civil Justice Reform

    This rule has been reviewed under E.O. 12988, Civil Justice Reform. 
Once the final rule is in effect, HHS/CDC notes that: (1) All State and 
local laws and regulations that are inconsistent with this rule will be 
preempted; (2) No retroactive effect will be given to this rule; and 
(3) Administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

E. EO 13132: Federalism

    HHS/CDC has reviewed this proposed rule in accordance with 
Executive Order 13132 regarding Federalism, and has determined that it 
does not have ``federalism implications.'' The rule does not ``have 
substantial direct effects on the States, on the relationship between 
the national government and the States, or on the distribution of power 
and responsibilities among the various levels of government.''
    In accordance with section 361(e) of the PHSA [42 U.S.C. 264(e)], 
nothing in this rule would supersede any provisions of State or local 
law except to the extent that such a provision conflicts with this 
rule.

F. Plain Language Act of 2010

    Under the Plain Language Act of 2010 (P.L. 111-274, October 13, 
2010), executive Departments and Agencies are required to use plain 
language in documents that explain to the public how to comply with a 
requirement the Federal Government administers or enforces. HHS/CDC has 
attempted to use plain language in promulgating this rule consistent 
with the Federal Plain Writing Act guidelines.

VI. References

    1. M. Maurin and D. Raoult. Q fever. Clin Microbiol Rev. Oct. 
1999;12(4):518-53.
    2. R. Eibach, F. Bothe, M. Runge, S. F. Fischer, W. Philipp, and 
M. Ganter. Q fever: baseline monitoring of a sheep and a goat flock 
associated with human infections. Epidemiol Infect. Nov. 2012 
140(11): 1939-1949.
    3. D.M. Waag. Coxiella burnetii: Host and bacterial responses to 
infection. Vaccine. Oct. 2007; 25 (42): 7288-7295.
    4. C. Rovery and D. Raoult. Meditteranean Spotted Fever. Infect 
Dis Clin N Am. Sept 2008. 22:515-530.
    5. D.H. Walker. Rickettsiae and rickettsial infections: the 
current state of knowledge. Clin Infect Dis. 2007 Jul 15. 45 Suppl 
1:S39-44.
    6. B.E. Ivins, J.W. Ezzell, J. Jemski, K.W. Hedlund, J.D. 
Ristroph, and S.H. Leppla. Immunization Studies with Attenuated 
Strains of Bacillus anthracis. Infection and Immunity. May 1986; 
52(2):454-458.
    7. Centers for Disease Control and Prevention, National Center 
for Emerging and Zoonotic Infectious Diseases ``Anthrax Sterne 
strain (34F2) of Bacillus anthracis,'' http://www.cdc.gov/nczved/divisions/dfbmd/diseases/anthrax_sterne/.
    8. Federal Select Agent Program, ``Select Agents and Toxins 
Exclusions,'' http://www.selectagents.gov/SelectAgentsandToxinsExclusions.html.
    9. C. Johnston, B. Martin, G. Fichant, P. Polard, and J.P. 
Claverys. Bacterial transformation: distribution, shared mechanisms 
and divergent control. Nature Rev. Microbiol. 2014; 12: 181-196.
    10. C. Lecaroz, M.J. Blanco-Prieto, M.A. Burrell. Intracellular 
killing of Brucella melitensis in human macrophages with 
microsphere-encapsulated gentamicin. J Antimicrob Chemother. 2006 
Sep. 58(3): 549-56.
    11. Biodefense Modeling Parameters Review Workshop, 2013: 
Ventura, California.
    12. E.A.E. Garber. Effects of Pasteurization on Detection and 
Toxicity of the Beans from Abrus precatorius, in Intentional and 
Unintentional Contaminants in Food and Feed. 2009, American Chemical 
Society. 143-151.
    13. E.A.E. Garber. Toxicity and detection of ricin and abrin in 
beverages. Journal of Food Protection, 2008. 71(9): 1875-1883.
    14. C. Millard. Final Recommendations to the CDC Select Agent 
Inter-Agency Workgroup from the Chairman of the Subcommittee on 
Toxins, Memorandum for Record, 2002.
    15. C.J. Malizio, M.C. Goodnough, and E.A. Johnson. Purification 
of Clostridium botulinum Type A Neurotoxin, in Bacterial Toxins: 
Methods and Protocols, O. Holst, Editor. 2000, Humana Press Inc.: 
Totowa, NJ.
    16. S. Sugii and G. Sakaguchi Molecular Construction of 
Clostridium-Botulinum Type-a Toxins. Infection and Immunity, 1975. 
12(6): 1262-1270.
    17. R. Wannernacher and B. Anderson. Inhalation Ricin: Aerosol 
Procedures, Animal Toxicology, and Therapy, Inhalation Toxicology 
2nd edition, 2006: 973--982.
    18. S. George. DHS Science and Technology Directorate Chemical-
Biological Defense Division (CBD), Biothreat Agent Factbook, August 
2010.
    19. Department of Defense, Office of the Surgeon General, US 
Army, Borden Institute. Medical Aspects of Biological Warfare. 2007. 
672.
    20. D.R. Franz and N.K. Jaax. Ricin Toxin, in Medical Aspects of 
Chemical and Biological Warfare, F.R. Sidell, E.T. Takafuji, and 
D.R. Franz, Editors. 1997, Office of The Surgeon General at TMM 
Publications: Washington, D.C. 631-642.
    21. R.W. Wannemacher and J.B. Anderson. Inhalation Ricin: 
Aerosol Procedures, Animal Toxicology, and Therapy. Inhalation 
Toxicology, 2007. 19(10): 873-887.
    22. F.E. Ahmed. Seafood Safety. 1991, Institute of Medicine. 
Committee on Evaluation of the Safety of Fishery Products: National 
Academy Press.
    23. A. Alfonso, M.C. Louzao, M.R. Vieytes, and L.M. Botana. 
Comparative-Study of the Stability of Saxitoxin and Neosaxitoxin in 
Acidic Solutions and Lyophilized Samples. Toxicon, 1994. 32(12): 
1593-1598.
    24. L.M. Botana, ed. Seafood and Freshwater Toxins, 
Pharmacology, Physiology and Detection. CRC Press: Boca Raton, FL.
    25. V.M. Bricelj and SW. Shumway. Paralytic shellfish toxins in 
bivalve molluscs: occurence, transfer kinetics, and 
biotransformation. Reviews in Fisheries Science, 1998. 6(4): 315-
383.
    26. W.D. Burrows and S.E. Renner. Biological warfare agents as 
threats to potable water. Environmental Health Perspectives, 1999. 
107(12): 975-984.
    27. J. Patockaa and L. Stredab, Brief review of natural 
nonprotein neurotoxins. ASA Newsletter, 2002. 89(16).
    28. C.E. Whalley. Toxins of Biological Origin, in CRDEC-SP-
0211990: Aberdeen Proving Ground, Maryland.
    29. S.A. Morse, R.A. Mah, and W.J. Dobrogosz, Regulation of 
staphylococcal enterotoxin B. J Bacteriol, 1969. 98(1): 4-9.
    30. H.D. Raj and M.S. Bergdoll, Effect of Enterotoxin B on Human 
Volunteers. Journal of Bacteriology, 1969. 98(2): 833-834.
    31. U.S. Department of Health and Human Services, National 
Institutes of Health. (2013). NIH Guidelines for Research Involving 
Recombinant Or Synthetic Nucleic Acid Molecules (NIH Guidelines). 
Available at: http://osp.od.nih.gov/sites/default/files/NIH_Guidelines.html.
    32. P. Thapa, M.J. Espiritu, C.C. Cabalteja, and J.P. Bingham. 
Conotoxins and their regulatory considerations. Regulatory and 
Toxicology and Pharmacology, July 2014. 70: 197-202.

[[Page 2814]]

List of Subjects in 42 CFR Part 73

    Biologics, Packaging and containers, Penalties, Reporting and 
recordkeeping requirements, Transportation.

    For the reasons discussed in the preamble, we propose to amend 42 
CFR part 73 as follows:

PART 73--SELECT AGENTS AND TOXINS

0
1. The authority citation for part 73 continues to read as follows:

    Authority:  42 U.S.C. 262a; sections 201-2014, 221 and 231 of 
Title II of Public Law 107-188, 116 Stat 637 (42 U.S.C. 262a).

0
2. Section 73.1 is amended by adding in alphabetical order, definitions 
of inactivation and kill curve to read as set forth below.


Sec.  73.1  Definitions.

* * * * *
    Inactivation means a method to render a select agent non-viable but 
retain characteristic of interest for future use, or to render any 
nucleic acids that can produce infectious forms of any select agent 
virus non-infectious for future use.
* * * * *
    Kill curve means the results of a dose-response experiment where a 
select agent is subjected to increasing amounts of the inactivating 
treatment to determine the minimum conditions required to render it 
non-viable or to render any nucleic acids that can produce infectious 
forms of any select agent virus as non-infectious.
* * * * *
0
3. Section 73.3 is amended as follows:
0
a. By revising paragraph (b).
0
b. By adding new paragraphs (d)(2)(i), (ii), and (iii).
0
c. By revising paragraphs (d)(3) introductory text and (d)(3)(i).
0
d. By redesignating paragraph (d)(5) as paragraph (d)(7).
0
e. By adding new paragraphs (d)(5), (d)(6), and (d)(8).
0
f. By adding paragraph (e)(3) to read as set forth below.
    The additions and revisions read as follows:


Sec.  73.3  HHS select agents and toxins.

* * * * *
    (b) HHS select agents and toxins:

Abrin
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Crimean-Congo hemorrhagic fever virus
Diacetoxyscirpenol
Eastern equine encephalitis virus
Ebola virus*
Francisella tularensis*
Lassa fever virus
Lujo virus
Marburg virus*
Monkeypox virus
Reconstructed replication competent forms of the 1918 pandemic 
influenza A virus containing any portion of the coding regions of all 
eight gene segments (Reconstructed 1918 influenza A virus)
Ricin
SARS coronavirus (SARS-CoV)
Saxitoxin
South American hemorrhagic fever viruses:
Chapare
Guanarito
Junin
Machupo
Sabia
Staphylococcal enterotoxins (subtypes A-E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
    Far Eastern subtype
    Siberian subtype
Kyasanur Forest disease virus
Omsk haemorrhagic fever virus
Variola major virus (Smallpox virus) *
Variola minor virus (Alastrim) *
Yersinia pestis*
* * * * *
    (d)* * *
    (2) Non-viable HHS select agents or nonfunctional HHS toxins.
    (i) Unless waived by the HHS Secretary, a select agent or regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that has been subjected to a validated inactivation process to 
remove viability or infectious form (i.e., the ability to reproduce or 
produce disease, while maintaining cellular structure) is not excluded 
from the requirements of this part until an individual or entity:
    (A) Develops a site-specific kill curve to define conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve must be developed 
for each strain that undergoes the inactivation procedure. A new kill 
curve must be created upon any change in procedure or inactivation 
equipment.
    (B) Develops site-specific standard operating inactivation 
procedures to ensure that the material is inactivated by a safety 
margin determined by the kill curve.
    (C) Subjects representative samples of inactivated select agents or 
any nucleic acids that can produce infectious forms of any select agent 
viruses to a validated sterility testing protocol to ensure that the 
inactivation method has rendered the select agent non-viable or 
regulated nucleic acids non-infectious.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was subjected to a validated inactivation protocol is 
reported to APHIS or CDC.
    (E) Reviews annually, and revises as necessary, the following:
    (1) The kill curve procedure and results;
    (2) Site-specific standard operating procedures to ensure that 
select agents or regulated nucleic acids that can produce infectious 
forms of any select agent virus are inactivated by a safety margin; and
    (3) The validated sterility testing protocol used to ensure that 
the inactivation method has rendered a select agent non-viable or 
regulated nucleic acids that can produce infectious forms of any select 
agent virus sample non-infectious.
    (F) Reviews, and revises as necessary, documents listed in 
paragraph (d)(2)(i)(E) of this section after any change in principal 
investigator, change in protocol, or any reported viability of a select 
agent or infectivity of regulated nucleic acids that can produce 
infectious forms of any select agent viruses previously assessed as 
inactive.
    (ii) Unless waived by the HHS Secretary, an extract from a select 
agent is not excluded from the requirements of this part until an 
individual or entity meets the following requirements:
    (A) Any extract is subjected to a process that removes all viable 
cells, spores, or virus particles.
    (B) Any extract is subjected to a validated sterility testing 
protocol to ensure that the inactivation method has rendered the 
extract free of a select agent.
    (C) Any viability of an extract that was subjected to a validated 
inactivation protocol is reported to the Responsible Official.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was previously assessed as inactive by their validated 
sterility testing protocol is reported to APHIS or CDC.
    (3) Except as required in Sec.  73.16(l), the aggregate amount of 
the toxin under the control of a principal investigator, treating 
physician or veterinarian, or commercial manufacturer or distributor 
does not, at any time, exceed the following amounts: 1000 mg of Abrin; 
1 mg of Botulinum neurotoxins; 10,000

[[Page 2815]]

mg of Diacetoxyscirpenol; 1000 mg of Ricin; 500 mg of Saxitoxin; 100 mg 
of Staphylococcal enterotoxins (subtypes A-E); 10,000 mg of T-2 toxin; 
or 500 mg of Tetrodotoxin.
    (i) The toxin is transferred only after the transferor uses due 
diligence and documents the identification of the recipient and the 
legitimate need (i.e., prophylactic, protective, bona fide research, or 
other peaceful purpose) claimed by the recipient to use such toxin. 
Information to be documented includes, but is not limited to, the 
recipient identity information, including the recipient's name, 
institution name, address, telephone number and email address; name of 
the toxin and the total amount transferred, and the legitimate need 
claimed by the recipient. Notwithstanding the provisions of paragraph 
(d) of this section, the HHS Secretary retains the authority to, 
without prior notification, inspect and copy or request the submission 
of the due diligence documentation to the CDC.
* * * * *
    (5) An HHS select toxin identified in an original food sample or 
clinical sample.
    (6) Select toxins that are produced as a byproduct in the study of 
the toxin producing host organism so long as the toxin has not been 
intentionally cultivated, collected, purified, or otherwise extracted, 
and the material containing the toxin is rendered non-functional and 
disposed of within 30 days of the initiation of the culture.
* * * * *
    (8) Waste generated during the delivery of patient care from a 
patient infected with a select agent that is decontaminated with a 
validated method within seven calendar days of the conclusion of 
patient care,
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary for reconsideration of a decision denying an application for 
the exclusion of an attenuated strain of a select agent or a select 
toxin modified to be less potent or toxic. The written request for 
reconsideration must state the facts and reasoning upon which the 
individual or entity relies to show the decision was incorrect. The HHS 
Secretary will grant or deny the request for reconsideration as 
promptly as circumstances allow and will state, in writing, the reasons 
for the decision.
* * * * *
0
4. Section 73.4 is amended as follows:
0
a. By revising paragraph (b).
0
b. By adding new paragraphs (d)(2)(i), (ii), and (iii).
0
c. By adding paragraph (d)(4).
0
d. By adding paragraph (e)(3).
    The revision and additions read as follows:


Sec.  73.4  Overlap select agents and toxins.

* * * * *
    (b) Overlap select agents and toxins:
Bacillus anthracis*
Burkholderia mallei*
Burkholderia pseudomallei*
Hendra virus
Nipah virus
Rift Valley fever virus
Venezuelan equine encephalitis virus
* * * * *
    (d) * * *
    (2) * * *
    (i) Unless waived by the APHIS Administrator or HHS Secretary, a 
select agent or regulated nucleic acids that can produce infectious 
forms of any select agent virus that has been subjected to a validated 
inactivation process to remove viability or infectious form (i.e., the 
ability to reproduce or produce disease, while maintaining cellular 
structure) is not excluded from the requirements of this part until an 
individual or entity:
    (A) Develops a site-specific kill curve to define conditions of 
inactivation for each select agent or regulated nucleic acids that can 
produce infectious forms of any select agent viruses. If there are 
strain-to-strain variations in resistance of a select agent to the 
inactivation procedure, then a specific kill curve must be developed 
for each strain that undergoes the inactivation procedure. A new kill 
curve must be created upon any change in procedure or inactivation 
equipment.
    (B) Develops site-specific standard operating inactivation 
procedures to ensure that the material is inactivated by a safety 
margin determined by the kill curve.
    (C) Subjects representative samples of inactivated select agents or 
nucleic acids that can produce infectious forms of any select agent 
viruses to a validated sterility testing protocol to ensure that the 
inactivation method has rendered a select agent non-viable or regulated 
nucleic acids non-infectious.
    (D) Reports any viability of a select agent or infectivity of 
regulated nucleic acids that can produce infectious forms of any select 
agent virus that was subjected to a validated inactivation protocol to 
the Responsible Official.
    (E) Reviews annually, and revises as necessary, the following:
    (1) The kill curve procedure and results;
    (2) Site-specific standard operating procedures to ensure that 
select agents or regulated nucleic acids that can produce infectious 
forms of any select agent viruses are inactivated by a safety margin; 
and
    (3) The validated sterility testing protocol used to ensure that 
the inactivation method has rendered a select agent non-viable or 
regulated nucleic acids that can produce infectious forms of any select 
agent viruses non-infectious.
    (F) Reviews, and revises as necessary, documents listed in 
paragraph (d)(2)(i)(E) of this section after any change in principal 
investigator, change in protocol, or any reported viability of a select 
agent or infectivity of regulated nucleic acids that can produce 
infectious forms of any select agent virus previously assessed as 
inactive.
    (ii) Unless waived by the APHIS Administrator or HHS Secretary, an 
extract from a select agent is not excluded from the requirements of 
this part until an individual or entity meets the following 
requirements:
    (A) Any extract is subjected to a process that removes all viable 
cells, spores, or virus particles.
    (B) Any extract is subjected to a validated sterility testing 
protocol to ensure that the inactivation method has rendered the 
extract free of a select agent.
    (C) Any viability of an extract that was subjected to a validated 
inactivation protocol is reported to the Responsible Official.
    (D) Any viability of a select agent or infectivity of regulated 
nucleic acids that can produce infectious forms of any select agent 
virus that was previously assessed as inactive by the validated 
sterility testing protocol is reported to APHIS or CDC.
    (d) * * *
    (4) Waste generated during the delivery of patient care from a 
patient infected with a select agent that is decontaminated with a 
validated method within seven calendar days of the conclusion of 
patient care.
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary or APHIS Administrator for reconsideration of a decision 
denying an application for the exclusion of an attenuated strain of a 
select agent or a select toxin modified to be less potent or toxic. The 
written request for reconsideration must state the facts and reasoning 
upon which the individual or entity relies to show the decision was 
incorrect. The HHS Secretary or APHIS Administrator will grant or deny 
the request for reconsideration as promptly as circumstances allow and 
will state, in writing, the reasons for the decision.
* * * * *

[[Page 2816]]

0
5. Section 73.5 is amended as follows:
0
a. By revising paragraph (a)(1).
0
b. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
c. By adding new paragraph (a)(3).
    The revisions and addition read as follows:


Sec.  73.5  Exemptions for HHS select agents and toxins.

    (a) * * *
    (1) Unless directed otherwise by the HHS Secretary, within seven 
calendar days after identification of the select agent and toxin 
(except for Botulinum neurotoxin and/or Staphylococcal enterotoxin 
(Subtypes A-E)), or within thirty calendar days after identification of 
Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E), 
the select agent or toxin is transferred in accordance with Sec.  73.16 
or destroyed on-site by a recognized sterilization or inactivation 
process,
* * * * *
    (3) Unless otherwise directed by the HHS Secretary, the clinical or 
diagnostic specimens collected from a patient infected with a select 
agent are transferred in accordance with Sec.  73.16 or destroyed on-
site by a recognized sterilization or inactivation process within seven 
days after delivery of patient care has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
6. Section 73.6 is amended as follows:
0
a. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
b. By adding paragraph (a)(3).
    The revision and addition read as follows:


Sec.  73.6  Exemptions for overlap select agents and toxins.

    (a) * * *
    (3) Unless otherwise directed by the HHS Secretary or 
Administrator, the clinical or diagnostic specimens collected from a 
patient infected with a select agent are transferred in accordance with 
Sec.  73.16 or destroyed on-site by a recognized sterilization or 
inactivation process within seven days after delivery of patient care 
has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within 7 calendar days after identification.
* * * * *
0
7. Section 73.7 is amended as follows:
0
a. By redesignating paragraphs (b) through (k) as paragraphs (c) 
through (l), respectively.
0
b. By adding a new paragraph (b) to read as follows:


Sec.  73.7  Registration and related security risk assessments.

* * * * *
    (b) As a condition of registration, each entity is required to be 
in compliance with the requirements of this part for select agents and 
toxins listed on the registration regardless of whether the entity is 
in actual possession of the select agent or toxin. With regard to 
toxins, the entity registered for possession, use or transfer of a 
toxin must be in compliance with the requirements of this part 
regardless of the amount of toxin currently in possession.
* * * * *
0
8. Section 73.9 is amended as follows:
0
a. In paragraph (a)(6) by removing ``laboratory'' and adding in its 
place ``registered space'' and adding ``and the corrections 
documented'' after ``corrected'' at the end of the sentence.
0
b. By adding paragraph (a)(7) to read as set forth below.


Sec.  73.9  Responsible Official.

    (a) * * *
    (7) Ensure that individuals are provided the contact information 
for the HHS or USDA Office of Inspector General Hotline so that they 
may anonymously report any safety or security concerns related to 
select agents and toxins.
* * * * *
0
9. Section 73.10 is amended by adding a new sentence to the end of 
paragraph (e) to read as follows:


Sec.  73.10  Restricting access to select agents and toxins; security 
risk assessments.

* * * * *
    (e) * * * A Responsible Official must immediately notify the 
Responsible Official of the visited entity if the person's access to 
select agents and toxins has been terminated.
* * * * *
0
10. Section 73.11 is amended as follows:
0
a. In paragraph (c)(5) by adding ``keycards,'' between ``keys,'' and 
``passwords'' and removing ``numbers'' and adding in its place 
``permissions''.
0
b. By adding paragraph (c)(11).
0
c. By adding paragraph (d)(7)(vi).
0
d. By adding a sentence to the end of paragraph (h).
    The additions read as follows:


Sec.  73.11  Security.

* * * * *
    (c) * * *
    (11) Describe how the entity authorizes the means of entry into 
areas where select agents or toxins are stored or used, to include 
centralized access control management systems (e.g., keycards) and/or 
mechanical key management.
    (d) * * *
    (7) * * *
    (vi) Any loss of computer, hard drive or other data storage device 
containing information that could be used to gain access to select 
agents or toxins.
* * * * *
    (h) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
11. Section 73.12 is amended as follows:
0
a. By revising paragraph (a).
0
b. By removing paragraph (c)(2), redesignating paragraph (c)(3) as 
(c)(2), and in newly redesignated paragraph (c)(2), removing ``NIH 
Guidelines for Research Involving Recombinant DNA Molecules'' and 
adding in its place ``NIH Guidelines for Research Involving Recombinant 
or Synthetic Nucleic Acid Molecules''.
0
c. By adding a new sentence to the end of paragraph (e).
    The revision and addition read as follows:


Sec.  73.12  Biosafety.

    (a) An individual or entity required to register under this part 
must develop and implement a written biosafety plan that is 
commensurate with the risk of the select agent or toxin, given its 
intended use. The biosafety plan must contain sufficient information 
and documentation to describe the biosafety and containment procedures 
for the select agent or toxin, including any animals (including 
arthropods) or plants intentionally or accidentally exposed to or 
infected with a select agent. Biosafety and containment procedures 
specific to each registered laboratory must be available to each 
individual working in that laboratory. The current biosafety plan must 
be submitted for initial registration, renewal of registration, or

[[Page 2817]]

when requested. The biosafety plan must include the following 
provisions:
    (1) A written risk assessment for each procedure involving a select 
agent or toxin that addresses the hazards associated with the agent or 
toxin.
    (i) The hazardous characteristics of each agent or toxin listed on 
the entity's registration, including probable routes of transmission in 
the laboratory and in the environment, infective dose (if known), 
stability in the environment, host range, contribution of any genetic 
manipulations, and endemicity.
    (ii) Hazards associated with laboratory procedures related to the 
select agent or toxin;
    (2) Safeguards in place with associated work practices to protect 
registered entity personnel, the public, and the environment from 
exposure to the select agent or toxin including, but not limited to: 
Safety training requirements for registered entity personnel performing 
the procedure; required personal protective equipment and other safety 
equipment; required containment equipment including, but not limited 
to, biological safety cabinets, animal caging systems, and centrifuge 
safety containers; and required engineering controls and other facility 
safeguards.
    (3) Written procedures for decontamination with a validated method, 
of all contaminated or potentially contaminated materials including, 
but not limited to: Cultures and other materials related to the 
propagation of select agents or toxins, items related to the analysis 
of select agents and toxins, personal protective equipment, animal 
caging systems and bedding, and animal carcasses or extracted tissues.
    (4) Written procedures for decontamination, with a validated 
method, of laboratory surfaces and equipment using manufacturer's 
specification.
    (5) Effluent decontamination procedures, with a validated method, 
that describe the treatment of effluent material contaminated with 
select agents and toxins.
    (6) Procedures to respond to emergencies such as spills, sharps 
injury, or animal bites involving select agents and toxins.
    (7) Procedures for the handling of select agents and toxins in the 
same spaces with non-select agents and toxins in order to prevent 
unintentional contamination.
* * * * *
    (e) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
12. Section 73.14 is amended as follows:
0
a. By adding a new sentence to the end of paragraph (a).
0
b. By adding a new sentence to the end of paragraph (f).
    The additions read as follows:


Sec.  73.14  Incident response.

    (a) * * * The current incident response plan must be submitted for 
initial registration, renewal of registration, or when requested.
* * * * *
    (f) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and all individuals who 
participated in the drill or exercise.
0
13. Section 73.15 is amended as follows:
0
a. In paragraph (a)(1) by removing ``before that individual has such 
access to select agents and toxins'' and adding in its place ``, within 
12 months of that individual's anniversary of receiving such approval 
or prior to his or her entry into an area where select agents or toxins 
are used or stored, whichever occurs first.''.
0
b. By adding paragraph (e) to read as set forth below.


Sec.  73.15  Training.

* * * * *
    (e) The Responsible Official must ensure and document that 
individuals are provided the contact information of the HHS or USDA 
Office of Inspector General Hotline so that they may anonymously report 
any safety or security concerns related to select agents and toxins.
0
14. Section 73.16 is amended by revising paragraph (l)(1) to read as 
follows:


Sec.  73.16  Transfers.

* * * * *
    (l) * * *
    (1) Transfer the amounts only after the transferor uses due 
diligence and documents that the recipient has a legitimate need (i.e., 
prophylactic, protective, bona fide research, or other peaceful 
purpose) to handle or use such toxins. Information to be documented 
includes, but is not limited, to the recipient information, toxin and 
amount transferred, and declaration that the recipient has legitimate 
purpose to store and use such toxins.
* * * * *
0
15. Section 73.17 is amended as follows:
0
a. In paragraphs (a)(1)(iii) and (a)(3)(v) by adding ``or other storage 
container'' after ``freezer''.
0
b. By adding paragraph (a)(1)(ix).
0
c. By adding paragraph (a)(8).
0
d . In paragraph (b) by adding ``legible,'' after ``are''.
0
e. By revising paragraph (c).
    The revision and additions read as follows:


Sec.  73.17  Records.

    (a) * * *
    (1) * * *
    (ix) If destroyed, the quantity (e.g., containers, vials, tubes, 
etc.) of select agent destroyed, the date of such action, and by whom.
* * * * *
    (8) For a select agent or an extract from a select agent that has 
been rendered non-viable or regulated nucleic acids that can produce 
infectious forms of any select agent virus that have been rendered non-
infectious through inactivation:
    (i) A written description of the inactivation process used for 
rendering a select agent non-viable or regulated nucleic acids that can 
produce infectious forms of any select agent virus non-infectious;
    (ii) The sterility testing protocol used to verify non-viability of 
a select agent or non-infectivity of regulated nucleic acids that can 
produce infectious forms of any select agent virus and the results of 
the test, including investigation, of any inactivation process failures 
and the corrective actions taken;
    (iii) The name of each individual performing the inactivation 
method and sterility testing protocols;
    (iv) The date(s) the inactivation method and sterility testing 
protocols were completed;
    (v) The location where the inactivated method and sterility testing 
protocols were performed; and
    (vi) An inactivation certificate that includes the date of 
inactivation, method of inactivation, date of final sterility testing 
protocol result, and the Principal Investigator. A copy of the 
inactivation certificate must accompany any transfer of inactivated 
material.
* * * * *
    (c) Any records that contain information related to the 
requirements of the regulations. Such records may include, but are not 
limited to, biocontainment certifications, laboratory notebooks, 
institutional biosafety and/or animal use committee minutes and 
approved protocols, and records associated with occupational

[[Page 2818]]

health and suitability programs. All records created under this part 
must be maintained for 3 years.
* * * * *

    Dated: January 12, 2016.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2016-00758 Filed 1-14-16; 4:15 pm]
 BILLING CODE 4163-18-P



                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                             2805

                                                      DEPARTMENT OF HEALTH AND                                Clifton Road NE., Atlanta, Georgia,                    populations that the commenter
                                                      HUMAN SERVICES                                          30329. Please call ahead to (404) 718–                 considers appropriate.
                                                                                                              2000 and ask for a representative from                    HHS/CDC also invites comments on
                                                      [Docket No. CDC–2015–0006]
                                                                                                              the Division of Select Agents and                      the following questions:
                                                      42 CFR Part 73                                          Toxins to schedule your visit.                            (1) Are there other methods that
                                                                                                              FOR FURTHER INFORMATION CONTACT: Dr.                   should be required to validate the
                                                      RIN 0920–AA59                                           Dan Sosin, Acting Director, Division of                rendering of a select agent non-viable or
                                                                                                              Select Agents and Toxins, Centers for                  regulated nucleic acids that can produce
                                                      Possession, Use, and Transfer of                                                                               infectious forms of any select agent
                                                                                                              Disease Control and Prevention, 1600
                                                      Select Agents and Toxins; Biennial                                                                             virus non-infectious?
                                                                                                              Clifton Road NE., MS–A46, Atlanta,
                                                      Review of the List of Select Agents and                                                                           (2) Should there be changes to the
                                                                                                              Georgia 30329. Telephone: (404) 718–
                                                      Toxins and Enhanced Biosafety                                                                                  toxin permissible limits for excluded
                                                                                                              2000.
                                                      Requirements                                                                                                   toxins?
                                                                                                              SUPPLEMENTARY INFORMATION:
                                                      AGENCY: Centers for Disease Control and                   The NPRM is organized as follows:                       (3) Should Diacetoxyscirpenol (DAS)
                                                      Prevention (CDC), Department of Health                                                                         and T–2 be removed from the select
                                                                                                              I. Public Participation                                toxin list because they do not have the
                                                      and Human Services (HHS).                               II. Background
                                                      ACTION: Notice of Proposed Rulemaking                                                                          potential to pose a severe threat to
                                                                                                                 A. Legal Authority
                                                      (NPRM).                                                    B. Historical background to this
                                                                                                                                                                     public health and safety?
                                                                                                                    rulemaking                                          (4) Does seven calendar days provide
                                                      SUMMARY:    In accordance with the Public               III. Summary of Proposed Changes to 42 CFR             a sufficient amount of time for the entity
                                                      Health Security and Bioterrorism                              part 73                                          to destroy or transfer the select agents or
                                                      Preparedness and Response Act of 2002                      A. Definitions                                      toxins after identification?
                                                      (the Bioterrorism Response Act), the                       B. Proposed changes to the list of select              (5) Are there any specific biosafety
                                                      Centers for Disease Control and                               agents                                           measures that should be required to
                                                      Prevention (CDC) in the Department of                      C. Inactivation of a Select Agent                   prevent laboratory acquired infections
                                                                                                                 D. Toxins                                           (LAIs) or accidental release of the select
                                                      Health and Human Services (HHS) has
                                                                                                                 E. Exemptions for select agents and toxins
                                                      reviewed the list of biological agents                     F. Registration
                                                                                                                                                                     agents and toxins from an entity into the
                                                      and toxins that have the potential to                      G. Responsible Official                             community?
                                                      pose a severe threat to public health and                  H. Visitor Access to Select Agents and                 (6) What alternative regulatory
                                                      safety and proposes to amend and                              Toxins                                           requirement could be constructed such
                                                      republish the list. Specifically, we are                   I. Security, Biosafety, and Incident                that a registered entity would know
                                                      proposing to remove six biological                            Response Plans                                   whether it had a theft or loss of a select
                                                      agents; add provisions to address the                      J. Training                                         agent or toxin without that registered
                                                      inactivation of select agents; add                         K. Records                                          entity first having ‘‘an accurate, current
                                                                                                              IV. Alternatives Considered                            inventory for each select agent . . . held
                                                      specific provisions to the section of the
                                                                                                              V. Required Regulatory Analyses
                                                      regulations addressing biosafety; and                      A. Executive Orders 12866 and 13563
                                                                                                                                                                     in long term storage’’?
                                                      clarify regulatory language concerning                     B. The Regulatory Flexibility Act                      Comments received, including
                                                      security, training, incident response,                     C. Paperwork Reduction Act of 1995                  attachments and other supporting
                                                      and records.                                               D. EO 12988: Civil Justice Reform                   materials, are part of the public record
                                                      DATES: Submit written or electronic                        E. EO 13132: Federalism                             and subject to public disclosure. Do not
                                                      comments by March 21, 2016.                                F. Plain Language Act of 2010                       include any information in your
                                                                                                              VI. References                                         comment or supporting materials that
                                                      ADDRESSES: You may submit comments,
                                                      identified by Docket No. CDC–2015–                      I. Public Participation                                you consider confidential or
                                                      0006 or RIN 0920–AA59 by any of the                                                                            inappropriate for public disclosure.
                                                                                                                 Interested persons or organizations                 HHS/CDC will carefully consider all
                                                      following methods:                                      are invited to participate in this
                                                         • Federal eRulemaking Portal: http://                                                                       comments submitted in preparation of a
                                                                                                              rulemaking by submitting written views,                final rule.
                                                      www.regulations.gov. Follow the                         recommendations, and data. Comments
                                                      instructions for submitting comments.                   are invited on any topic related to this               II. Background
                                                         • Mail: Division of Select Agents and                rulemaking.
                                                      Toxins, Centers for Disease Control and                                                                        A. Legal Authority
                                                                                                                 In addition, HHS/CDC invites
                                                      Prevention, 1600 Clifton Road NE., MS–                  comments specifically as to whether                      HHS/CDC is promulgating this rule
                                                      A46, Atlanta, Georgia 30329, Attn:                      there are biological agents or toxins that             under the authority of sections 201–204
                                                      Docket CDC–2015–0006.                                   should be added or removed from the                    and 221 of Title II of Public Law 107–
                                                         Instructions: All submissions received               HHS list of select agents and toxins                   188, 116 Stat 637 (42 U.S.C. 262a).
                                                      must include the agency name and                        based on the following criteria:
                                                      docket number or Regulatory                                                                                    B. Historical Background to This
                                                                                                                 (1) The effect on human health of                   Rulemaking
                                                      Information Number (RIN) for this                       exposure to the agent or toxin;
                                                      rulemaking. All relevant comments                          (2) The degree of contagiousness of                   Subtitle A of the Public Health
                                                      received will be posted without change                  the agent or toxin and the methods by                  Security and Bioterrorism Preparedness
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      to http://regulations.gov, including any                which the agent or toxin is transferred                and Response Act of 2002, (42 U.S.C.
                                                      personal information provided. For                      to humans;                                             262a), requires HHS to regulate the
                                                      access to the docket to read background                    (3) The availability and effectiveness              possession, use, and transfer of
                                                      documents or comments received, go to                   of pharmacotherapies and                               biological agents or toxins that have the
                                                      http://www.regulations.gov.                             immunizations to treat and prevent any                 potential to pose a severe threat to
                                                         Comments will also be available for                  illness resulting from infection by the                public health and safety (select agents
                                                      public inspection from Monday through                   agent or exposure to the toxin; and                    and toxins). Subtitle B of the Public
                                                      Friday, except for legal holidays, from 9                  (4) Any other criteria, including the               Health Security and Bioterrorism
                                                      a.m. to 5 p.m., Eastern Time, at 1600                   needs of children and other vulnerable                 Preparedness and Response Act of 2002


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00044   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2806                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      (which may be cited as the Agricultural                 agents and toxins) are those regulated by              proposed based on comments received
                                                      Bioterrorism Protection Act of 2002), (7                HHS under the authority of the                         to the advance notice of proposed
                                                      U.S.C. 8401), requires the United States                Bioterrorism Response Act and also                     rulemaking (80 FR 10656) referenced
                                                      Department of Agriculture (USDA) to                     regulated by the U.S. Department of                    above, recommendations from the
                                                      regulate the possession, use, and                       Agriculture under the authority of the                 ISATTAC, information from the DHS
                                                      transfer of biological agents or toxins                 Agricultural Bioterrorism Protection Act               Material Threat Determinations (DHS–
                                                      that have the potential to pose a severe                of 2002 (7 U.S.C. 8401).                               MTD) of biological agents and toxins
                                                      threat to animal or plant health, or                       The Bioterrorism Response Act                       (https://
                                                      animal or plant products (select agents                 requires the HHS Secretary to review                   www.medicalcountermeasures.gov/
                                                      and toxins). Accordingly, HHS and                       and republish the list of select agents                phemce/dhs.aspx), and the expertise of
                                                      USDA have promulgated regulations                       and toxins on at least a biennial basis.               federal agencies and staff responsible for
                                                      requiring individuals or entities that                  Using government subject matter                        the oversight of the possession, use, and
                                                      possess, use, or transfer select agents                 experts, HHS/CDC conducts the                          transfer of select agents and toxins. We
                                                      and toxins to register with the CDC or                  biennial review process in consultation                are also proposing specific changes to
                                                      the Animal and Plant Health Inspection                  with the HHS/CDC Intragovernmental                     the current regulations, as discussed
                                                      Service (APHIS). See 42 CFR part 73, 7                  Select Agents and Toxins Technical                     below, addressing biosafety; clarifying
                                                      CFR part 331, and 9 CFR part 121 (the                   Advisory Committee (ISATTAC). The                      regulatory language concerning security,
                                                      select agent regulations). The Federal                  ISATTAC is comprised of Federal                        training, incident response, and records;
                                                      Select Agent Program (FSAP) is the                      government employees from CDC,                         correcting an omission from the
                                                      collaboration of the CDC, Division of                   Biomedical Advanced Research and                       technical amendment (appeal process
                                                      Select Agents and Toxins (DSAT) and                     Development Authority (BARDA)                          for exclusion); and revision of the select
                                                      the APHIS Agriculture Select Agent                      within the Office of the Assistant                     agent list with current taxonomic
                                                      Services (AgSAS) to administer the                      Secretary for Preparedness and                         names.
                                                      select agent regulations in a manner that               Response, the National Institutes of
                                                                                                              Health (NIH), the Food and Drug                        A. Definitions
                                                      minimizes the administrative burden on
                                                      persons subject to the select agent                     Administration (FDA), the Department                      We are proposing to add two new
                                                      regulations. The FSAP administers the                   of Homeland Security (DHS), the                        terms to section 73.1 (Definitions) of the
                                                      select agent regulations in close                       Department of Defense (DOD), the                       regulations. We are proposing to define
                                                      coordination with the Federal Bureau of                 USDA/Animal and Plant Health                           the term ‘‘Inactivation’’ as ‘‘a method to
                                                      Investigation’s Criminal Justice                        Inspection Service (APHIS), USDA/                      render a select agent non-viable but
                                                      Information Services Division (CJIS).                   Agricultural Research Service (ARS),                   retain characteristic of interest for future
                                                         The Bioterrorism Response Act also                   and USDA Center for Veterinary                         use, or to render any nucleic acids that
                                                      requires the HHS Secretary to establish                 Biologics (CVB). Based on the criteria                 can produce infectious forms of any
                                                      by regulation a list of biological agents               outlined in the Bioterrorism Response                  select agent virus non-infectious for
                                                      and toxins that have the potential to                   Act, the ISATTAC considered the                        future use.’’ We are also proposing to
                                                      pose a severe threat to public health and               following criteria in their review of the              define the term ‘‘Kill curve’’ as ‘‘the
                                                      safety. In determining whether to                       HHS and Overlap lists of select agents                 results of a dose-response experiment
                                                      include an agent or toxin on the list, the              and toxins: The degree of pathogenicity                where a select agent is subjected to
                                                      HHS Secretary considers criteria such as                (ability of an organism to cause disease),             increasing amounts of the inactivating
                                                      the effect on human health of exposure                  communicability (ability to spread from                treatment to determine the minimum
                                                      to an agent or toxin; the degree of                     infected to susceptible hosts), ease of                conditions required to render it non-
                                                      contagiousness of the agent and the                     dissemination, route of exposure,                      viable or to render any nucleic acids
                                                      methods by which the agent or toxin is                  environmental stability, ease of                       that can produce infectious forms of any
                                                      transferred to humans; the availability                 production in the laboratory, ability to               select agent virus as non-infectious.’’
                                                      and effectiveness of pharmacotherapies                  genetically manipulate or alter, long-                 The new definitions will help clarify
                                                      and immunizations to treat and prevent                  term health effects, acute morbidity                   proposed regulatory language in section
                                                      illnesses resulting from an agent or                    (illness), mortality, available treatment,             73.12 (Biosafety).
                                                      toxin; and the needs of children and                    status of host immunity, vulnerability of
                                                                                                                                                                     B. Proposed Changes to the List of Select
                                                      other vulnerable populations. The                       special populations, and the burden or
                                                                                                                                                                     Agents
                                                      current list of HHS select agents and                   impact on the health care system.
                                                      toxins can be found at 42 CFR 73.3                         On February 27, 2015, HHS/CDC                          On February 27, 2015, HHS/CDC
                                                      (HHS select agents and toxins) and 42                   published an advance notice of                         published an advance notice of
                                                      CFR 73.4 (Overlap select agents and                     proposed rulemaking (80 FR 10656) in                   proposed rulemaking (ANPRM) (80 FR
                                                      toxins). The list of HHS and Overlap                    which we requested public comment on                   10656) in which we requested public
                                                      select agents and toxins is also available              (1) whether there are biological agents                comment specifically on whether there
                                                      at: http://www.selectagents.gov/                        or toxins that should be added or                      are biological agents or toxins that
                                                      SelectAgentsandToxinsList.html.                         removed from the HHS list of select                    should be added or removed from the
                                                         The HHS Secretary last republished                   agents and toxins; and (2) whether HHS/                HHS list of select agents and toxins.
                                                      the list of HHS select agents and toxins                CDC should remove the following six                       In that same docket, HHS/CDC also
                                                      in the Federal Register on October 5,                   select agents from the HHS list of select              requested public comments as to
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      2012 (77 FR 61084). The list of HHS                     agents and toxins: Coxiella burnetti,                  whether biological agents specifically
                                                      select agents and toxins is divided into                Rickettsia prowazekii, Bacillus                        listed in the February 27, 2015 ANPRM
                                                      two sections. The select agents and                     anthracis Pasteur strain, Brucella                     should be removed or remain on the list.
                                                      toxins listed in section 73.3 (HHS select               abortus, Brucella melitensis, and                      The listed agents were Coxiella burnetti,
                                                      agents and toxins) are those regulated                  Brucella suis.                                         Rickettsia prowazekii, Bacillus
                                                      only by HHS under the authority of the                                                                         anthracis Pasteur strain, Brucella
                                                      Bioterrorism Response Act (42 U.S.C.                    III. Summary of Proposed Changes                       abortus, Brucella melitensis, and
                                                      262a). The select agents and toxins                        The following changes to the list of                Brucella suis. We are now proposing
                                                      listed in section 73.4 (Overlap select                  HHS select agents and toxins are                       that these agents be removed from the


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00045   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                             2807

                                                      HHS list of select agents based on the                  threat to public health and safety. We                 Bacillus anthracis Pasteur Strain (42
                                                      twenty-two comments received in                         are, however, still seeking comment                    CFR 73.4)
                                                      response to the February 27, 2015                       from those who may believe that C.                        We received six comments to the
                                                      ANPRM, recommendations from the                         burnetii remains a severe threat to                    February 27, 2015 ANPRM with all
                                                      ISATTAC, and our review of current                      public health and safety and                           commenters agreeing that Bacillus
                                                      scientific data regarding these biological              accordingly should be retained as a HHS                anthracis Pasteur strain should not be
                                                      agents.                                                 select agent.                                          included as a select agent based on B.
                                                      Coxiella burnetii (42 CFR 73.3)                         Rickettsia prowazekii (42 CFR 73.3)                    anthracis Pasteur strain lacks the
                                                                                                                                                                     plasmid that encodes the toxin genes
                                                         In response to the February 27, 2015                    In response to the February 27, 2015                causing disease. The B. anthracis Sterne
                                                      ANPRM, we received 11 comments                          ANPRM, we received eight comments                      strain, which lacks the plasmid that
                                                      concerning Coxiella burnetii. Only two                  concerning Rickettsia prowazekii. Only                 encodes for the capsule, was excluded
                                                      commenters recommended that C.                          one commenter recommended to retain                    from the requirements of the regulations
                                                      burnetii remain on the list because                     Rickettsia prowazekii because                          effective on February 27, 2003.
                                                      ‘‘antibiotic treatment should not be                    ‘‘antibiotic treatment should not be                      The ISATTAC recommended the
                                                      considered for removing the agent.’’ The                considered for removing the agent.’’ The               removal of B. anthracis Pasteur strain
                                                      other nine commenters argued that C.                    other seven commenters supported                       from the overlap list of select agents and
                                                      burnetii should not be included as a                    removal based on the following reasons:                toxins because:
                                                      select agent based on the following                        • The risk of mass casualties is low                   • B. anthracis Pasteur strain lacks the
                                                      assertions:                                             because R. prowazekii can be treated                   plasmid that encodes the toxin genes
                                                         • Five commenters stated it is not                   with a single dose of doxycycline when                 causing disease (Ref. 6);
                                                      easily transmitted from person to                       symptoms are present;                                     • B. anthracis Sterne strain, which
                                                      person.                                                                                                        lacks the plasmid that encodes for the
                                                         • Three commenters referenced that                      • Transmissibility from person to
                                                                                                              person is low due to the fact that R.                  capsule, was excluded from the
                                                      even in the absence of antibiotic                                                                              requirements of the regulations effective
                                                      treatment, Q fever (the disease with                    prowazekii is usually transmitted via
                                                                                                              blood, although it can be spread through               on February 27, 2003 (Ref. 7–8); and
                                                      acute and chronic stages caused by the                                                                            • Historically, the B. anthracis
                                                      bacteria C. burnetii) is generally a self-              inhalation of louse feces;
                                                                                                                                                                     Pasteur strain has been retained as a
                                                      limited flu-like illness with low                          • The agent has poor environmental                  select agent to allow for continued
                                                      mortality (Ref. 1).                                     stability; and                                         oversight of laboratories in which the
                                                         • All commenters acknowledged that                      • The difficulty in growing and                     accidental (or intentional) combination
                                                      most infections are inapparent and most                 purifying substantial quantities of these              of this strain with the Sterne strain
                                                      seropositive individuals cannot                         agents in vitro.                                       could occur to produce de novo the wild
                                                      remember an infection consistent with                      The ISATTAC recommended the                         type phenotype B. anthracis. However,
                                                      Q fever.                                                removal of R. prowazekii from the HHS                  a recent study indicates that bacterial
                                                         • Six commenters agreed that                         list of select agents and toxins because:              transformation of B. subtilis with
                                                      Coxiella is susceptible to a number of                     • It is treatable with available                    plasmid DNA is inefficient; indicating
                                                      readily available antibiotics. Preferred                antibiotics (Ref. 4 and 5);                            that transformation with plasmid pXO1
                                                      treatments include tetracycline or                         • The risk of mass casualties is low                into closely related bacteria such as the
                                                      doxycycline. Quinolones have also been                  because R. prowazekii can be treated                   Bacillus anthracis Pasteur strain would
                                                      used successfully and Co-trimoxazole is                 with a single dose of doxycycline when                 also be inefficient (Ref. 9).
                                                      recommended in specific situations                      symptoms are present (Ref. 4 and 5);                      We agreed with the commenters and
                                                      such as pregnancy.                                      and                                                    ISATTAC. We propose to remove B.
                                                         The ISATTAC recommended the                                                                                 anthracis Pasteur strain because the
                                                      removal of C. burnetii from the HHS list                   • Transmissibility from person to
                                                                                                                                                                     transformation of a virulence plasmid
                                                      of select agents and toxins because:                    person is low due to the fact that R.
                                                                                                                                                                     from one Bacillus strain to another is
                                                         • It has a low mortality rate with                   prowazekii is usually transmitted via
                                                                                                                                                                     difficult.
                                                      antibiotic treatment and most                           blood, although it can be spread through
                                                      seropositive individuals cannot                         inhalation of louse feces (Ref. 5).                    Brucella abortus, B. melitensis, and B.
                                                      remember an infection consistent with                      We are now proposing to remove R.                   suis (42 CFR 73.4)
                                                      Q fever (Ref. 2); and                                   prowazekii from the HHS list of select                    Responses were received from 16
                                                         • A whole-cell killed vaccine (Q-Vax)                agents (42 CFR 73.3). As discussed                     commenters to the February 27, 2015
                                                      with nearly 100% efficacy is licensed in                above, our proposal is supported by the                ANPRM, that addressed the retention of
                                                      Australia and has been used to                          comments we received in response to                    the three Brucella species (B. abortus, B.
                                                      vaccinate U.S. researchers whom were                    the February 27, 2015 ANPRM and the                    melitensis, and B. suis) currently on the
                                                      at risk (Ref. 3).                                       recommendations of the ISATTAC. Both                   overlap select agent list. Only two
                                                         We are now proposing to remove C.                    the commenters and the ISATTAC                         commenters recommended to retain
                                                      burnetii from the HHS list of select                    supported their recommendations with                   these species because ‘‘antibiotic
                                                      agents (42 CFR 73.3). As discussed                      the scientific references noted above.                 treatment should not be considered for
                                                      above, our proposal is supported by                     We further conclude that, based on                     removing the agent.’’ The other 14
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      comments we received in response to                     recent information provided by DHS–                    commenters supported removal based
                                                      the February 27, 2015 ANPRM and the                     MTD, R. prowazekii does not pose a                     on the rationale provided in the
                                                      recommendations of the ISATTAC. Both                    severe threat to public health and safety.             ANPRM.
                                                      the commenters and the ISATTAC                          We are, however, still seeking comment                    The ISATTAC recommended the
                                                      supported their recommendations with                    from those who may believe that R.                     removal of B. abortus, B. melitensis, and
                                                      the scientific references noted above.                  prowazekii remains a severe threat to                  B. suis from the overlap list of select
                                                      We further conclude that, based on                      public health and safety and                           agents and toxins because:
                                                      recent information provided by DHS–                     accordingly should be retained as a HHS                   • B. abortus has a low human
                                                      MTD, C. burnetii does not pose a severe                 select agent.                                          mortality rate (Ref. 10);


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00046   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2808                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                         • B. abortus, B. melitensis, and B.                  to be created upon any change in                       the toxin exclusion provision to require
                                                      suis are treatable with antibiotics (Ref.               procedure or inactivation equipment. In                the transferor to document the identity
                                                      10); and                                                addition, a validated sterility testing                of the recipient and the legitimate need
                                                         • Human-to-human transmission is                     protocol to ensure that the inactivation               (i.e., prophylactic, protective, bona fide
                                                      extremely rare, and wildlife carriers in                method has rendered a select agent non-                research, or other peaceful purpose)
                                                      the United States often come into                       viable or regulated nucleic acids that                 claimed by the transferee. Information
                                                      contact with humans without significant                 can produce infectious forms of any                    required to be documented would also
                                                      transmission (Ref. 10).                                 select agent virus non-infectious would                include the name of the toxin and the
                                                         We agreed with the commenters and                    be required to be conducted.                           total amount transferred. Identity
                                                      ISATTAC. We propose to remove B.                          We are also proposing that written                   information of the person requesting
                                                      abortus, B. melitensis, and B. suis                     records be kept for a select agent or                  and using the toxins would include the
                                                      because although Brucella has a low                     extracts that have been subjected to a                 individual’s name, institution name,
                                                      infectious dose, it is treated, mortality is            procedure to render them non-viable or                 address, telephone number, and email
                                                      low, efficacy of treatment is good for all              regulated nucleic acids that can produce               address.
                                                      three Brucella strains.                                 infectious forms of any select agent
                                                                                                              virus that have been subjected to a                    Toxin Permissible Limits
                                                      C. Inactivation of a Select Agent
                                                                                                              procedure to render them non-
                                                         We are proposing to add specific                     infectious.                                               In conjunction with this biennial
                                                      requirements to the biosafety section of                  We are also soliciting ideas as to                   review, the FSAP solicited input from
                                                      the regulations (42 CFR 73.12) to                       whether there are other methods that                   biological toxin subject matter experts to
                                                      address the requirements for rendering                  should be required to validate the                     review the listed exclusion limits for
                                                      a select agent or an nucleic acids that                 rendering of a select agent non-viable or              select toxins in the HHS select agent
                                                      can produce infectious forms of any                     regulated nucleic acids that can produce               regulations. To assess the amount
                                                      select agent virus ‘‘non-viable.’’                      infectious forms of any select agent                   necessary to weaponize a biological
                                                         Sections 73.3 (HHS select agents and                 virus non-infectious.                                  toxin, DHS developed toxin parameters
                                                      toxins) and 73.4 (Overlap select agents                                                                        and attack scenarios for potential
                                                      and toxins) both provide that a ‘‘non-                  D. Toxins                                              inhalation and ingestion exposures to
                                                      viable’’ select agent is excluded from the              Due Diligence                                          select toxins. DHS used the formulas
                                                      requirements of the select agent                                                                               described below to estimate ingestion
                                                                                                                 Section 73.3(d)(3) of the select agent
                                                      regulations. We are proposing that for                                                                         scenarios while employing the ‘‘NIST
                                                                                                              regulations (42 CFR 73.(d)(3))specifies
                                                      an agent to be ‘‘non-viable,’’ or to render             the select toxin amounts under the                     CONTAM Multizone Modeling’’
                                                      a nucleic acids that can produce                        control of a principal investigator,                   software (http://www.bfrl.nist.gov/
                                                      infectious forms of any select agent                    treating physician or veterinarian, or                 IAQanalysis/) for inhalation scenarios.
                                                      virus non-infectious for future use, an                 commercial manufacturer or distributor                 To estimate the amount of toxin for each
                                                      entity must use a validated method. A                   that are excluded from the requirements                scenario, DHS analyzed a range of
                                                      validated method means that the                         of the select agent regulations. However,              release sizes (in mg) for each biological
                                                      method must be scientifically sound                     this exclusion applies to the transfer of              toxin in order to estimate the number of
                                                      such that method will produce                           select toxins ‘‘only after the transferor              people that would be exposed to LD–50
                                                      consistent results each time the method                 uses due diligence and documents that                  (lethal dose, 50% or median lethal dose,
                                                      is used. As outlined in our guidance for                the recipient has a legitimate need . . .              the amount of the substance required
                                                      ‘‘Non-viable Select Agents and                          to handle or use such toxins’’ (42 CFR                 (usually per body weight) to kill 50% of
                                                      Nonfunctional Select Toxins and                         73.3(d)(3)(i)). This provision was added               the test population); or TD–50 (the
                                                      Rendering Samples Free of Select                        to the select agent regulations to address             median toxic dose of a toxin is the dose
                                                      Agents and Toxins’’ (http://                            the concern that someone might be able                 at which toxicity occurs in 50% of
                                                      www.selectagents.gov/guidance-                          to covertly stockpile toxins by receiving              cases) levels of each toxin amount by
                                                      nonviable.html), an inactivation                        multiple orders below the excluded                     ingestion of milk (using published TD–
                                                      procedure may include (1) use of the                    amount. The toxin ‘‘due diligence’’                    50 or LD–50) and/or indoor inhalation
                                                      exact conditions of an accepted method                  provision requires a person transferring               (using published LD–50). The inhalation
                                                      that has been validated, such as                        toxins in amounts which would                          models analyzed toxin releases in three
                                                      autoclaving, (2) a published method                     otherwise be excluded from the                         different indoor public facilities that
                                                      with adherence to the exact published                   provisions to: (1) Use due diligence to                experience heavy commuter volume
                                                      conditions, or (3) for in-house methods,                assure that the recipient has a legitimate             (population details for these facilities
                                                      validation testing should include the                   need to handle or use such toxins; and                 are given in Table 1). One hundred
                                                      specific conditions used and                            (2) report to the FSAP if they detect a                scenarios were generated for each
                                                      appropriate controls.                                   known or suspected violation of Federal                facility using 1–10mm particle sizes. The
                                                         As part of the inactivation procedure,               law or become aware of suspicious                      models used 10 random locations
                                                      an entity would be required to develop                  activity related to the toxin.                         within each facility (potential release
                                                      a site specific kill curve to identify                     ‘‘Due diligence’’ is generally                      locations and population evenly spaced
                                                      conditions of inactivation for each select              understood to be such a measure of                     throughout occupied area) at 10 random
                                                      agent or regulated nucleic acids that can
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                                                                              prudence, activity, or assiduity, as is                times. The inhalation models assumed:
                                                      produce infectious forms of any select                  properly to be expected from, and                         • No immediate symptoms, so no
                                                      agent virus. If there are strain-to-strain              ordinarily exercised by, a reasonable                  changes in population movement due to
                                                      variations in resistance of a select agent              and prudent person under the particular                attack
                                                      to the inactivation procedure, then a                   circumstances; not measured by any
                                                      specific kill curve would be required to                absolute standard, but depending on the                   • Respiration rate 10L/min
                                                      be developed for each strain that                       relative facts of the specific case.                      • All people assumed to have the
                                                      undergoes the inactivation procedure. A                    We are proposing to add a more                      same mass = 70 kg (e.g., did not account
                                                      new kill curve would also be required                   specific documentation requirement to                  for lower doses required for children)



                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00047   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                                            2809

                                                                                                TABLE 1—SUMMARY OF FACILITY POPULATION AND RESIDENCE TIMES
                                                                                                                                                                                                                         Simulation
                                                                                                                                                                                         2008 Annual     Simulation       transient
                                                                                                                                                                                          passenger       transient
                                                                                                                 Facility                                                                                                  average
                                                                                                                                                                                            traffic         hourly     residence time
                                                                                                                                                                                           (people)      population       (minutes)

                                                      High throughput transportation facilities ......................................................................................    255,500,000         43,750              10
                                                      High throughput transportation facilities ......................................................................................    219,000,000         37,500              15
                                                      High throughput transportation facilities ......................................................................................     64,300,000         11,005              60



                                                         The ingestion models investigated                               equals the number of grams of toxin                              have the potential to pose a severe
                                                      biological toxins introduced into a fluid                          available divided by the toxin                                   threat to public health and safety or
                                                      (e.g., milk) that was purchased and                                concentration). For example, for a 1 g                           whether these two toxins should be
                                                      consumed by consumers over a two day                               attack, with a toxin that has an LD–50                           removed from the select toxin list given
                                                      period. Production details and specifics                           of 1mg/kg, the volume of milk                                    the high exclusion limit for DAS and T–
                                                      of how the toxins were introduced were                             contaminated would be 1000 mg/(0.056                             2.
                                                      not considered. In particular, the largest                         mg/mL*1000 mL/L) = 18 L of milk.
                                                                                                                            • For small attack sizes, it is assumed                       Proposed Removal of Select Toxins
                                                      scenarios involve contaminating greater
                                                      than ten million servings, which was                               the attacker would target appropriately-                         Short, Paralytic Alpha-Conotoxins
                                                      determined to be implausible in                                    sized small holding tanks or containers,                           We are proposing short, paralytic
                                                      practice. The ingestion models made the                            while for large attack sizes, the attacker                       alpha-conotoxins containing the
                                                      following assumptions:                                             would target large holding tanks or                              following amino acid sequence
                                                         • Milk containing specified quantity                            silos.                                                           (X1CCX2PACGX3X4X5X6CX7) be
                                                      of active toxin (1 mg to 1 kg) reaches                                • If the toxin is degraded due to                             removed as a select toxin for the
                                                      store shelves.                                                     pasteurization or storage, the amount of                         following reasons:
                                                         • Milk is consumed over six days at                             toxin introduced pre-processing would                              • The DHS model reported LD–50
                                                      a uniform rate.                                                    have to be correspondingly larger than                           value for inhalation delivery of alpha-
                                                         • Contaminated milk is consumed                                 these masses.                                                    conotoxin is 20 mg/kg, which is a low
                                                      daily until supply is depleted or a
                                                                                                                         Proposed Increase of Regulatory                                  toxicity compared to other select toxins;
                                                      health advisory is issued.
                                                         • Milk contamination discovered and                             Exclusion Limits                                                   • A regulatory exclusion limit of
                                                      health advisory issued a minimum of                                   Based on the data generated by the                            10,000 mg would require the depletion
                                                      one day, and a maximum of >1 week                                  models described above, we are                                   of the cone snail population to achieve
                                                      post attack (at which point all                                    proposing the following exclusion limits                         this quantity.
                                                      contaminated milk has been consumed).                              based on the amounts estimated to                                  Therefore, based on the low toxicity
                                                         • For toxins other than saxitoxin and                           expose less than 10 people by inhalation                         of short, paralytic alpha-conotoxins and
                                                      tetrodotoxin, the attacker chooses a                               or less than 100 people by ingestion to                          the high dosage required for inhalation
                                                      toxin concentration such that a person                             the LD–50 or TD–50 levels of toxin:                              exposure, we are proposing that the
                                                      in the 45+ years old age group will                                   • Increase the regulatory exclusion                           alpha-conotoxin be removed from the
                                                      consume 1 LD–50 (or TD–50) over 6 day                              limit of Botulinum neurotoxin (BoNT)                             select toxin list (Ref. 32).
                                                      consumption period.                                                from 0.5 mg to 1 mg;                                             Toxins: Exclusion of Original Food
                                                         • Since saxitoxin and tetrodotoxin are                             • Increase the regulatory exclusion                           Samples and Clinical Samples
                                                      largely excreted in approximately one                              limit of Staphylococcal enterotoxins
                                                      day after consumption, the attacker                                from 5 mg to 100 mg;                                                Original food samples and clinical
                                                      chooses a saxitoxin or tetrodotoxin                                   • Increase the regulatory exclusion                           samples are those specimens that are
                                                      concentration such that a person in the                            limit of saxitoxin from 100 mg to 500                            submitted to laboratories for diagnosis
                                                      45+ years old age group will consume                               mg;                                                              or verification purposes to identify or
                                                      1 LD–50 (or TD–50) over a one day                                     • Increase the regulatory exclusion                           verify a biological agent or toxin. For
                                                      consumption period.                                                limit of tetrodotoxin from 100 mg to 500                         example, an original food sample could
                                                         • Total volume of milk contaminated                             mg;                                                              be a container of potato salad or juice.
                                                      equals the number of grams of toxin                                   • Increase the regulatory exclusion                           An original clinical sample could be
                                                      available divided by the toxin                                     limit of abrin from 100 mg to 1,000 mg;                          serum or stool from a patient.
                                                      concentration (i.e., total volume of milk                             • Increase the regulatory exclusion                           Laboratories that test food sample and
                                                      contaminated depends on the mass of                                limit of ricin from 100 mg to 1,000 mg;                          clinical samples for the presence of
                                                      toxin assumed to be available (which                               and                                                              toxins generally do not know the level
                                                      varies from 1 mg to 1 kg) and the toxin                               • Increase the regulatory exclusion                           of toxin in a sample and do not extract
                                                      ingestion LD–50 (or TD–50)).                                       limit of DAS from 1,000 mg to 10,000                             and purify a toxin as part of their
                                                         • If the toxin ingestion LD–50 (or TD–                          mg.                                                              studies. Therefore, we are proposing to
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      50) is given by a range, the geometric                                • Increase the regulatory exclusion                           exclude the original food sample or
                                                      mean of this range is used.                                        limit of T–2 from 1,000 mg to 10,000                             clinical sample identified to contain an
                                                         • Range of total volumes of milk                                mg.                                                              HHS select toxin to be consistent with
                                                      contaminated is less than 1 L to                                      We are, however, still seeking                                the rationale for the current exclusion
                                                      approximately 108 L.                                               comment from those who may believe                               for animals exposed to toxins (42 CFR
                                                         • The amount of milk contaminated                               that we should retain the current                                73.3(d)(4)). The proposed exclusion is
                                                      is assumed to depend on how much                                   exclusion limits. In addition, we are                            based upon input from biological toxin
                                                      toxin the attacker has available (i.e., the                        interested in receiving comments from                            subject matter experts and our
                                                      total volume of milk contaminated                                  the public on whether DAS and T–2                                determination that quantifying the


                                                 VerDate Sep<11>2014       15:55 Jan 15, 2016     Jkt 238001     PO 00000      Frm 00048      Fmt 4702     Sfmt 4702     E:\FR\FM\19JAP1.SGM    19JAP1


                                                      2810                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      amount of toxin in these samples is                     toxin and meet all applicable select                   enterotoxin (Subtypes A–E)), or within
                                                      problematic because (1) the amount of                   agent and toxin regulatory requirements.               thirty calendar days after identification
                                                      toxin is highly variable, which would                                                                          of Botulinum neurotoxin and/or
                                                                                                              E. Exemptions for Select Agents and
                                                      require large amounts of food and                                                                              Staphylococcal enterotoxin (Subtypes
                                                                                                              Toxins
                                                      clinical samples to quantify or purify,                                                                        A–E), the select agent or toxin is
                                                      (2) laboratory procedures to extract                    Informing Specimen Provider                            transferred in accordance with § 73.16
                                                      toxin from samples are inefficient with                    Since a registered or certified                     or destroyed on-site by a recognized
                                                      most extractions producing low yields;                  reference laboratory typically confirms                sterilization or inactivation process,’’
                                                      (3) the resources that would be required                the identification of a select agent or
                                                      to quantify toxins in clinical samples                                                                         Patient Care
                                                                                                              toxin for public health and agriculture,
                                                      and food samples make sample
                                                                                                              clinical and diagnostic laboratories, we                  To clarify how the select agent
                                                      quantification prohibitively expensive;
                                                                                                              are proposing to require the registered                regulations apply to activities associated
                                                      and (4) procedures in these laboratories,
                                                                                                              or certified reference laboratory inform               with the diagnosis and care for
                                                      based on the requirements of their
                                                                                                              the specimen provider of the                           individuals infected with a select agent
                                                      public health mission, are designed only
                                                                                                              identification. This will ensure that the              or exposure to a select toxin, we are
                                                      for toxin detection and not for
                                                                                                              reference laboratory notifies the                      proposing to add provisions that HHS/
                                                      purification and quantification.
                                                                                                              specimen provider of the identification                CDC will not regulate material
                                                      Therefore, we are interested in
                                                                                                              of the select agent or toxin so that the               containing a select agent or toxin when
                                                      comments regarding our rationale that
                                                                                                              specimen provider is aware that they are               it is in a patient care setting and is not
                                                      the original food sample or clinical
                                                      sample identified to contain an HHS                     in possession of the agent or toxin and                being otherwise collected, tested or
                                                      select toxin should be excluded from                    must meet the requirements outlined in                 retained for non-patient care purposes.
                                                      the select agent regulation.                            42 CFR 73.5, 73.6.                                     However, once delivery of patient care
                                                                                                              Identification of Toxin                                for an illness associated with a select
                                                      Exclusion of Toxin Produced as a                                                                               agent or toxin has concluded these
                                                      Byproduct                                                  Once a clinical or diagnostic
                                                                                                                                                                     specimens would become subject to the
                                                         Laboratories that are only registered                laboratory has identified a select toxin-
                                                                                                                                                                     regulatory requirements. An entity
                                                      for BoNT-producing species of                           positive specimen, an APHIS/CDC Form
                                                                                                                                                                     unable to meet all of the regulatory
                                                      Clostridium do not normally have a                      4 (Report of the Identification of a Select
                                                                                                                                                                     requirements necessary to retain the
                                                      need to account for BoNT produced                       Agent or Toxin) must be submitted to
                                                                                                              the FSAP. The select agent regulations                 material will then have the option of
                                                      during the culturing of Clostridium                                                                            transferring the material containing the
                                                      since studying the toxin is not part of                 currently require the laboratory to
                                                                                                              transfer or destroy the material within                select agent or toxin in accord with the
                                                      their work objective. Therefore, we                                                                            select agent regulations or destroying
                                                      propose to exclude toxins that are                      seven days of identification (42 CFR
                                                                                                              73.5(a), 73.6(a)) because we determined                the materials within seven calendar
                                                      produced only as a byproduct to a study                                                                        days of the conclusion of patient care.
                                                      of the toxin producing host organism so                 through input from technical experts
                                                      long as the toxin has not been                          that the seven calendar days provides a                   We also are proposing to clarify that
                                                      intentionally collected, purified, or                   sufficient amount of time for the entity               FSAP does not regulate waste generated
                                                      otherwise extracted, and the material                   to destroy or transfer the select agents or            during the delivery of patient care.
                                                      containing the toxin is inactivated and                 toxins after identification. In the past,
                                                                                                              we have received comments that argued                  F. Registration
                                                      properly disposed of within 30 days of
                                                      the initiation of the culture. The 30 day               that the seven day requirement for                       We are codifying in regulations the
                                                      disposal time was recommended by                        transferring or destroying select agents               current FSAP policy that an entity is
                                                      biological toxin subject matter experts                 or toxins used for diagnosis or testing is             required to meet all of the regulatory
                                                      based on the time it would take to grow                 too short a time limit. Therefore, we are              requirements for those select agents and
                                                      the organism and perform the extraction                 seeking comments to determine if seven                 toxins listed on the entity’s registration
                                                      process. This exclusion allows                          calendar days provides a sufficient                    regardless of whether the select agent or
                                                      laboratories whose purpose does not                     amount of time for the entity to destroy               toxin is in the actual possession of the
                                                      include purification of the toxin to more               or transfer the select agents or toxins
                                                                                                                                                                     entity; and without regard to the actual
                                                      effectively conduct outbreak                            after identification.
                                                                                                                                                                     amounts of toxins in the possession of
                                                      investigations, food studies, and                          In addition, we are seeking comments
                                                                                                                                                                     the entity.
                                                      molecular characterization of agents                    to extend the exemption time period to
                                                      which produce toxin. In the case of                     30 days for BoNT and Staphylococcal                    G. Responsible Official (RO)
                                                      BoNT, these laboratories would still be                 enterotoxin (Subtypes A–E) to allow
                                                      regulated for the BoNT-producing                        clinical and diagnostic laboratories                     Section 73.9(a)(6) of the select agent
                                                      species of Clostridium and in the case                  sufficient time to complete their                      regulations currently states that the
                                                      of all other HHS select toxins the                      investigations without having to transfer              Responsible Official must ensure that an
                                                      laboratories would be regulated if they                 or destroy the sample. Laboratories                    annual inspection is conducted for each
                                                      wished to keep the material containing                  would still be required to report the                  laboratory where select agents and
                                                      toxins for longer than 30 days from the                 identification of BoNT immediately and                 toxins are stored or used. This
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      initiation of culture of the toxin                      Staphylococcal enterotoxin (Subtypes                   requirement also provides that the
                                                      producing host organism. If at any time                 A–E) within seven days. We are                         results of each inspection must be
                                                      an entity manipulated the material that                 proposing to amend the language in 42                  documented, and any deficiencies
                                                      contains the select toxin, such as                      CFR 73.5(a), and 42 CFR 73.6(a)to read:                identified during an inspection must be
                                                      intentional collection, purification or                 ‘‘Unless directed otherwise by the HHS                 corrected. We are adding a requirement
                                                      extraction of the toxin from culture                    Secretary, within seven calendar days                  that the Responsible Official must also
                                                      supernatant, such activities would void                 after identification of the select agent               document the corrective actions taken
                                                      this exemption, and the entity would be                 and toxin (except for Botulinum                        by the entity to address any identified
                                                      required to be registered for the select                neurotoxin and/or Staphylococcal                       deficiencies.


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00049   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                            2811

                                                      HHS or USDA Office of the Inspector                        • An incident response plan that                    I provides guidelines for work with
                                                      General Hotline                                         provides for measures that the registered              toxins of biological origin, we have
                                                         In response to a recommendation in                   entity will implement in the event of                  removed the reference to the OSHA
                                                      the December 2014 Federal Experts                       theft, loss, or release of a select agent or           regulations in 29 CFR 1910.1200 and
                                                      Security Advisory Panel report, we are                  toxin; inventory discrepancies; security               1910.1450. It should be noted that
                                                                                                              breaches (including information                        regulated entities must still meet the
                                                      adding a requirement that the
                                                                                                              systems); severe weather and other                     OSHA regulatory requirements where
                                                      Responsible Official must ensure that
                                                                                                              natural disasters; workplace violence;                 applicable.
                                                      individuals are provided the contact                                                                              In addition, we want to ensure that
                                                                                                              bomb threats and suspicious packages;
                                                      information of the HHS or USDA Office                                                                          laboratory personnel that are working
                                                                                                              and emergencies such as fire, gas leak,
                                                      of Inspector General Hotline so that                                                                           with select agents and toxins are aware
                                                                                                              explosion, power outage, etc. The
                                                      individuals are able to anonymously                                                                            of the risks associated with these agents.
                                                                                                              response procedures must account for
                                                      report a safety or security concern                                                                            As such, we are proposing to add a
                                                                                                              hazards associated with the select agent
                                                      related to select agents and toxins. In its                                                                    requirement that a laboratory-specific
                                                                                                              or toxin and appropriate actions to
                                                      December 2014 report, the Federal                                                                              biosafety manual must be accessible to
                                                                                                              contain such agent or toxin. (42 CFR
                                                      Experts Security Advisory Panel                         73.14)                                                 individuals. This is consistent with
                                                      recommended adding a specific                              Drills or exercises must be conducted               guidance provided by the CDC/NIH
                                                      requirement to include how individuals                  at least annually to test and evaluate the             publication, Biosafety in Microbiological
                                                      are informed so that they can access the                effectiveness of the plans. The plans                  and Biomedical Laboratories. This
                                                      HHS or USDA Office of Inspector                         must be reviewed and revised, as                       requirement is proposed to foster an
                                                      General Hotline to anonymously report                   necessary, after any drill or exercise and             enhanced culture of responsibility by
                                                      a safety or security concern.                           after any incident. We are proposing to                ensuring that appropriate biosafety
                                                      H. Visitor Access to Select Agents and                  require that these drills or exercises be              resources are available to all staff with
                                                      Toxins                                                  documented to include how the drill or                 access to select agents and toxins within
                                                                                                              exercise tested and evaluated the plan,                a select agent laboratory.
                                                         Section 73.10(e) of the select agent                 any problems identified and corrective                    The current regulations require that
                                                      regulations currently provides that a                   actions that were taken, and the names                 the biosafety plan be written using
                                                      person with a valid approval from the                   of the individuals who participated in                 performance standards. In the aftermath
                                                      HHS Secretary or APHIS Administrator                    the drill or exercise. This will provide               of recent biosafety incidents involving
                                                      to have access to select agents and                     a more thorough accounting of required                 select agents, we are proposing that the
                                                      toxins may request, through his or her                  activities via testing and entity-directed             biosafety plan should be designed
                                                      Responsible Official, that the HHS                      improvements.                                          according to a site-specific risk
                                                      Secretary or APHIS Administrator                           Similar to the existing requirement for             assessment in accordance with the risk
                                                      provide their approved access status to                 the security plan, we are also proposing               of a select agent, given its intended use
                                                      another registered individual or entity                 to add a requirement that the biosafety                by adding specific provisions to the
                                                      for a specified period of time. This                    and incident response plans be                         biosafety section that would require a
                                                      allows a scientist registered to work                   submitted for initial registration,                    written risk assessment for each
                                                      with a select agent at a registered entity              renewal of registration, or when                       registered select agent or toxin; written
                                                      to work with the select agent at another                requested by FSAP.                                     safety procedures to protect entity
                                                      registered entity. To ensure that the                                                                          personnel, the public, and the
                                                      Responsible Official of the entity                      Biosafety
                                                                                                                                                                     environment from exposure to the select
                                                      hosting the visitor is aware if a visiting                We are proposing to amend the                        agent or toxin; written decontamination
                                                      individual loses approval for access to                 regulatory language in section 73.12 to                procedures; and written waste
                                                      select agents and toxins, we are                        update the name change of the National                 management procedures.
                                                      proposing to add a requirement that the                 Institutes of Health (NIH) Guidelines for                 The FSAP would also like to solicit
                                                      Responsible Official at the home entity                 Research Involving Recombinant or                      ideas regarding any specific biosafety
                                                      must immediately notify the                             Synthetic Nucleic Acid Molecules (Ref.                 measures that should be required to
                                                      Responsible Official of the visiting                    31).                                                   prevent LAIs or accidental or
                                                      entity if the person’s access to select                   Prior to the publication of the 5th                  intentional release of the select agents
                                                      agents or toxins has been terminated.                   edition of CDC/NIH Biosafety in                        and toxins from an entity into the
                                                                                                              Microbiological and Biomedical                         community.
                                                      I. Security, Biosafety, and Incident                    Laboratories (Ref. 3), the Occupational
                                                      Response Plans                                          Safety and Health Administration                       Security
                                                        The select agent regulations require a                (OSHA) regulations in 29 CFR                              We are proposing to amend the
                                                      registered entity to develop and                        1910.1200 and 1910.1450 provided                       requirement that the security plan
                                                      implement a number of plans in order                    specific requirements for handling                     contain a description of how the entity
                                                      to ensure the safety and security of the                hazardous chemicals in the laboratories.               authorizes the means of entry into areas
                                                      select agents they handle. These are:                   This regulation also provided                          where select agents or toxins are stored
                                                        • A security plan that provides for                   recommendations for safely working                     or used, to include a requirement that
                                                      measures sufficient to safeguard the                    with chemical including toxins and                     the security plan must include a
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      select agent or toxin against                           gave non-mandatory recommendations                     description of centralized access control
                                                      unauthorized access, theft, loss, or                    for prudent practices in laboratories                  management systems (e.g., keycards)
                                                      release (42 CFR 73.11);                                 handling chemical hazards. As such, we                 and/or key management (mechanical
                                                        • A biosafety plan that provides for                  included this reference for entities to                keys).
                                                      measures sufficient to contain the select               consider when developing biosafety                        Paragraphs (d)(7)(i) through (d)(7)(v)
                                                      agent or toxin (e.g., physical structure                plans for those facilities working with                of section 11 of the select agent
                                                      and features of the entity, and                         toxins. Since the current edition of the               regulations encompass a list of events
                                                      operational and procedural safeguards)                  CDC/NIH Biosafety in Microbiological                   that individuals with access approval
                                                      (42 CFR 73.12); and                                     and Biomedical Laboratories Appendix                   from the APHIS Administrator or the


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00050   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2812                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      HHS Secretary must immediately report                   long-term storage to include the                       V. Required Regulatory Analyses
                                                      to the Responsible Official. We are                     quantity (i.e., number of vials) of select
                                                                                                                                                                     A. Executive Orders 12866 and 13563
                                                      proposing to add a new requirement                      agent destroyed, the date of such action,
                                                      that the Responsible Official must be                   and by whom.                                              Under Executive Order 12866 (EO
                                                      notified of any loss of computer, hard                                                                         12866), Regulatory Planning and Review
                                                                                                                 Section 73.17 of the select agent                   (58 FR 51735, October 4, 1993) HHS/
                                                      drive, or other data storage device
                                                                                                              regulations currently states that records              CDC is required to determine whether
                                                      containing information that could be
                                                                                                              and databases need to be accurate. To                  this regulatory action would be
                                                      used to gain access to select agents or
                                                      toxins. We believe that such notification               ensure that handwritten records are                    ‘‘significant’’ and therefore subject to
                                                      will facilitate notification of the Federal             accurate, we are proposing to clarify                  review by the Office of Management and
                                                      Bureau of Investigation if deemed                       that hand-written record must be legible               Budget (OMB) and the requirements of
                                                      necessary by the Responsible Official as                (i.e., capable of being read).                         the Executive Orders. This order defines
                                                      the loss of such equipment may be                          We are proposing to expand the scope                ‘‘significant regulatory action’’ as any
                                                      criminal in nature.                                     of records required to be maintained to                regulatory action that is likely to result
                                                                                                              include any records that contain                       in a rule that may:
                                                      J. Training                                                                                                       • Have an annual effect on the
                                                                                                              information related to the requirements
                                                         We are proposing to amend section 15                 of the regulations. Such records may                   economy of $100 million or more or
                                                      of the select agent regulations which                   include, but would not limited to,                     adversely affect in a material way the
                                                      concerns the provision of training for                  biocontainment certifications,                         economy, a sector of the economy,
                                                      staff and visitors who work in or visit                 laboratory notebooks, institutional                    productivity, competition, jobs, the
                                                      areas where select agents or toxins are                 biosafety and/or animal use committee                  environment, public health or safety, or
                                                      handled or stored. Since individuals                    minutes and approved protocols, and                    state, local, or tribal governments or
                                                      need to understand hazards associated                                                                          communities;
                                                                                                              records associated with occupational
                                                      with the select agents and toxins that                                                                            • Create a serious inconsistency or
                                                                                                              health and suitability programs. We
                                                      they will be working with in the                                                                               otherwise interfere with an action taken
                                                                                                              propose revision to the regulations will
                                                      laboratory or are in the area they will be                                                                     or planned by another agency;
                                                      visiting, we are proposing to require that              enhance the ability of FSAP to evaluate                   • Materially alter the budgetary
                                                      all individuals who have received                       biosafety, security, and incident                      impact of entitlements, grants, user fees,
                                                      approval to have access to select agents                response programs and includes any                     or loan programs or the rights and
                                                      and toxins have training that address                   record created under sections 73.5, 73.7,              obligations of recipients; or,
                                                      the particular needs of the individual                  73.9, 73.11, 73.12, 73.14, 73.15, 73.16,                  • Raise novel legal or policy issues
                                                      and the risks posed by the select agent                 73.17, and 73.19 of the select agent                   arising out of legal mandates, the
                                                      or toxin regardless of whether they have                regulations.                                           President’s priorities, or the principles
                                                      access to the select agents or toxins. The              Records for Long-term Storage                          set forth in EO 12866.
                                                      training would have to be completed                                                                               Executive Order 13563 (EO 13563),
                                                      within 12 months of that individual’s                      The FSAP continues to receive                       Improving Regulation and Regulatory
                                                      anniversary of receiving access approval                comments that are critical of that                     Review, (76 FR 3821, January 21, 2011),
                                                      or prior to his or her entry into an area               portion of the select agent regulations                updates some of the provisions of EO
                                                      where any select agents and toxins are                  that require a registered entity to                    12866 in order to promote more
                                                      used or stored, whichever occurs first.                 maintain ‘‘an accurate, current                        streamlined regulatory actions. This EO
                                                      This change is necessary in order to                    inventory for each select agent . . . held             charges, in part, that, while protecting
                                                      codify our policy regarding which                       in long term storage.’’ The comments                   ‘‘public health, welfare, safety, and our
                                                      individuals at registered entities are                  typically focus on the belief that a                   environment’’ that regulations must also
                                                      required to receive training.                           container based inventory requirement                  ‘‘promote predictability and reduce
                                                         We are also proposing to add a new                   is not useful to track inventory of                    uncertainty’’ in order to promote
                                                      paragraph (e) to section 15, which                      biological agents of which small                       economic growth. Further, regulations
                                                      would require the entity’s Responsible                  amounts of samples from the container                  must be written in plain language and
                                                      Official to provide contact information                 could be stolen without detection and                  be easy to understand.
                                                      for the USDA or HHS Office of the                                                                                 HHS/CDC has determined that this
                                                                                                              used to grow larger quantities. In the
                                                      Inspector General Hotline. Details of the                                                                      NPRM is a significant regulatory action
                                                                                                              Public Health Security and Bioterrorism
                                                      proposed addition may be found under                                                                           as defined in EO 12866. However, the
                                                                                                              Preparedness and Response Act of 2002,
                                                      the heading ‘‘Responsible Official.’’                                                                          Office of Management and Budget has
                                                                                                              Congress requires the Secretaries of
                                                                                                                                                                     waived their review of the document.
                                                      K. Records                                              Health and Human Services and
                                                        Based on inspections of registered                    Agriculture to include in the select                   B. The Regulatory Flexibility Act (RFA),
                                                      entities, we observed that entities are                 agent regulations a requirement for ‘‘the              as Amended by the Small Business
                                                      maintaining records of the destruction                  prompt notification of the Secretary,                  Regulatory Enforcement Fairness Act
                                                      of select agents even though section                    and appropriate Federal, State, and local              (SBREFA)
                                                      73.17 of the select agent regulations                   law enforcement agencies, of the theft or                 We have examined the impacts of the
                                                      currently does not include a                            loss of listed agents and toxins.’’ HHS/               proposed rule under the Regulatory
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      requirement for documenting when a                      CDC is soliciting ideas on any                         Flexibility Act (5 U.S.C. 601–612).
                                                      select agent is destroyed. To ensure the                alternative regulatory requirement that                Unless we certify that the proposed rule
                                                      proper tracking of a select agent from                  could be constructed such that a                       is not expected to have a significant
                                                      acquisition to destruction and to                       registered entity would know whether it                economic impact on a substantial
                                                      incorporate into the regulations what                   had a theft or loss of a select agent or               number of small entities, the Regulatory
                                                      entities are currently doing, we are                    toxin without that registered entity first             Flexibility Act (RFA), as amended by
                                                      proposing to add the requirement for                    having ‘‘an accurate, current inventory                the Small Business Regulatory
                                                      records to be created and maintained for                for each select agent . . . held in long               Enforcement Fairness Act (SBREFA),
                                                      the destruction of a select agent held in               term storage.’’                                        requires agencies to analyze regulatory


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00051   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                                 2813

                                                      options that would minimize any                         F. Plain Language Act of 2010                             15. C.J. Malizio, M.C. Goodnough, and E.A.
                                                      significant economic impact of a rule on                                                                       Johnson. Purification of Clostridium
                                                                                                                Under the Plain Language Act of 2010                 botulinum Type A Neurotoxin, in Bacterial
                                                      small entities. We certify that this                    (P.L. 111–274, October 13, 2010),                      Toxins: Methods and Protocols, O. Holst,
                                                      proposed rule will not have a significant               executive Departments and Agencies are                 Editor. 2000, Humana Press Inc.: Totowa, NJ.
                                                      economic impact on a substantial                        required to use plain language in                         16. S. Sugii and G. Sakaguchi Molecular
                                                      number of small entities within the                     documents that explain to the public                   Construction of Clostridium-Botulinum
                                                      meaning of the RFA.                                     how to comply with a requirement the                   Type-a Toxins. Infection and Immunity,
                                                        This regulatory action is not a major                 Federal Government administers or                      1975. 12(6): 1262–1270.
                                                                                                                                                                        17. R. Wannernacher and B. Anderson.
                                                      rule as defined by Sec. 804 of the Small                enforces. HHS/CDC has attempted to                     Inhalation Ricin: Aerosol Procedures, Animal
                                                      Business Regulatory Enforcement                         use plain language in promulgating this                Toxicology, and Therapy, Inhalation
                                                      Fairness Act of 1996. This proposed rule                rule consistent with the Federal Plain                 Toxicology 2nd edition, 2006: 973—982.
                                                      will not result in an annual effect on the              Writing Act guidelines.                                   18. S. George. DHS Science and
                                                      economy of $100,000,000 or more; a                                                                             Technology Directorate Chemical-Biological
                                                                                                              VI. References                                         Defense Division (CBD), Biothreat Agent
                                                      major increase in cost or prices; or
                                                      significant adverse effects on                             1. M. Maurin and D. Raoult. Q fever. Clin           Factbook, August 2010.
                                                                                                              Microbiol Rev. Oct. 1999;12(4):518–53.                    19. Department of Defense, Office of the
                                                      competition, employment, investment,                                                                           Surgeon General, US Army, Borden Institute.
                                                      productivity, innovation, or on the                        2. R. Eibach, F. Bothe, M. Runge, S. F.
                                                                                                              Fischer, W. Philipp, and M. Ganter. Q fever:           Medical Aspects of Biological Warfare. 2007.
                                                      ability of United States-based                                                                                 672.
                                                                                                              baseline monitoring of a sheep and a goat
                                                      companies to compete with foreign-                      flock associated with human infections.                   20. D.R. Franz and N.K. Jaax. Ricin Toxin,
                                                      based companies in domestic and                         Epidemiol Infect. Nov. 2012 140(11): 1939–             in Medical Aspects of Chemical and
                                                      export markets.                                         1949.                                                  Biological Warfare, F.R. Sidell, E.T. Takafuji,
                                                                                                                 3. D.M. Waag. Coxiella burnetii: Host and           and D.R. Franz, Editors. 1997, Office of The
                                                      C. Paperwork Reduction Act of 1995                      bacterial responses to infection. Vaccine. Oct.        Surgeon General at TMM Publications:
                                                                                                              2007; 25 (42): 7288–7295.                              Washington, D.C. 631–642.
                                                        In accordance with section 3507(d) of                                                                           21. R.W. Wannemacher and J.B. Anderson.
                                                                                                                 4. C. Rovery and D. Raoult. Meditteranean
                                                      the Paperwork Reduction Act of 1995                     Spotted Fever. Infect Dis Clin N Am. Sept              Inhalation Ricin: Aerosol Procedures, Animal
                                                      (44 U.S.C. 3501 et seq.), HHS/CDC has                   2008. 22:515–530.                                      Toxicology, and Therapy. Inhalation
                                                      determined that the Paperwork                              5. D.H. Walker. Rickettsiae and rickettsial         Toxicology, 2007. 19(10): 873–887.
                                                      Reduction Act does apply to                                                                                       22. F.E. Ahmed. Seafood Safety. 1991,
                                                                                                              infections: the current state of knowledge.
                                                                                                                                                                     Institute of Medicine. Committee on
                                                      information collection and                              Clin Infect Dis. 2007 Jul 15. 45 Suppl 1:S39–
                                                                                                                                                                     Evaluation of the Safety of Fishery Products:
                                                      recordkeeping requirements included in                  44.
                                                                                                                                                                     National Academy Press.
                                                      this rule. We note that the information                    6. B.E. Ivins, J.W. Ezzell, J. Jemski, K.W.
                                                                                                                                                                        23. A. Alfonso, M.C. Louzao, M.R. Vieytes,
                                                      collection and recordkeeping                            Hedlund, J.D. Ristroph, and S.H. Leppla.               and L.M. Botana. Comparative-Study of the
                                                                                                              Immunization Studies with Attenuated
                                                      requirements are already approved by                                                                           Stability of Saxitoxin and Neosaxitoxin in
                                                                                                              Strains of Bacillus anthracis. Infection and           Acidic Solutions and Lyophilized Samples.
                                                      the Office of Management and Budget                     Immunity. May 1986; 52(2):454–458.
                                                      (OMB) under OMB Control Number                                                                                 Toxicon, 1994. 32(12): 1593–1598.
                                                                                                                 7. Centers for Disease Control and                     24. L.M. Botana, ed. Seafood and
                                                      0920–0576.                                              Prevention, National Center for Emerging and           Freshwater Toxins, Pharmacology,
                                                                                                              Zoonotic Infectious Diseases ‘‘Anthrax Sterne
                                                      D. EO 12988: Civil Justice Reform                                                                              Physiology and Detection. CRC Press: Boca
                                                                                                              strain (34F2) of Bacillus anthracis,’’ http://         Raton, FL.
                                                         This rule has been reviewed under                    www.cdc.gov/nczved/divisions/dfbmd/                       25. V.M. Bricelj and SW. Shumway.
                                                                                                              diseases/anthrax_sterne/.                              Paralytic shellfish toxins in bivalve molluscs:
                                                      E.O. 12988, Civil Justice Reform. Once
                                                                                                                 8. Federal Select Agent Program, ‘‘Select           occurence, transfer kinetics, and
                                                      the final rule is in effect, HHS/CDC                    Agents and Toxins Exclusions,’’ http://
                                                      notes that: (1) All State and local laws                                                                       biotransformation. Reviews in Fisheries
                                                                                                              www.selectagents.gov/                                  Science, 1998. 6(4): 315–383.
                                                      and regulations that are inconsistent                   SelectAgentsandToxinsExclusions.html.                     26. W.D. Burrows and S.E. Renner.
                                                      with this rule will be preempted; (2) No                   9. C. Johnston, B. Martin, G. Fichant, P.           Biological warfare agents as threats to potable
                                                      retroactive effect will be given to this                Polard, and J.P. Claverys. Bacterial                   water. Environmental Health Perspectives,
                                                      rule; and (3) Administrative proceedings                transformation: distribution, shared                   1999. 107(12): 975–984.
                                                      will not be required before parties may                 mechanisms and divergent control. Nature                  27. J. Patockaa and L. Stredab, Brief review
                                                      file suit in court challenging this rule.               Rev. Microbiol. 2014; 12: 181–196.                     of natural nonprotein neurotoxins. ASA
                                                                                                                 10. C. Lecaroz, M.J. Blanco-Prieto, M.A.            Newsletter, 2002. 89(16).
                                                      E. EO 13132: Federalism                                 Burrell. Intracellular killing of Brucella                28. C.E. Whalley. Toxins of Biological
                                                                                                              melitensis in human macrophages with                   Origin, in CRDEC–SP–0211990: Aberdeen
                                                         HHS/CDC has reviewed this proposed                   microsphere-encapsulated gentamicin. J                 Proving Ground, Maryland.
                                                      rule in accordance with Executive Order                 Antimicrob Chemother. 2006 Sep. 58(3):                    29. S.A. Morse, R.A. Mah, and W.J.
                                                      13132 regarding Federalism, and has                     549–56.                                                Dobrogosz, Regulation of staphylococcal
                                                      determined that it does not have                           11. Biodefense Modeling Parameters                  enterotoxin B. J Bacteriol, 1969. 98(1): 4–9.
                                                      ‘‘federalism implications.’’ The rule                   Review Workshop, 2013: Ventura, California.               30. H.D. Raj and M.S. Bergdoll, Effect of
                                                                                                                 12. E.A.E. Garber. Effects of Pasteurization        Enterotoxin B on Human Volunteers. Journal
                                                      does not ‘‘have substantial direct effects
                                                                                                              on Detection and Toxicity of the Beans from            of Bacteriology, 1969. 98(2): 833–834.
                                                      on the States, on the relationship                      Abrus precatorius, in Intentional and                     31. U.S. Department of Health and Human
                                                      between the national government and                     Unintentional Contaminants in Food and                 Services, National Institutes of Health.
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      the States, or on the distribution of                   Feed. 2009, American Chemical Society.                 (2013). NIH Guidelines for Research
                                                      power and responsibilities among the                    143–151.                                               Involving Recombinant Or Synthetic Nucleic
                                                      various levels of government.’’                            13. E.A.E. Garber. Toxicity and detection of        Acid Molecules (NIH Guidelines). Available
                                                         In accordance with section 361(e) of                 ricin and abrin in beverages. Journal of Food          at: http://osp.od.nih.gov/sites/default/files/
                                                                                                              Protection, 2008. 71(9): 1875–1883.                    NIH_Guidelines.html.
                                                      the PHSA [42 U.S.C. 264(e)], nothing in                    14. C. Millard. Final Recommendations to               32. P. Thapa, M.J. Espiritu, C.C. Cabalteja,
                                                      this rule would supersede any                           the CDC Select Agent Inter-Agency                      and J.P. Bingham. Conotoxins and their
                                                      provisions of State or local law except                 Workgroup from the Chairman of the                     regulatory considerations. Regulatory and
                                                      to the extent that such a provision                     Subcommittee on Toxins, Memorandum for                 Toxicology and Pharmacology, July 2014. 70:
                                                      conflicts with this rule.                               Record, 2002.                                          197–202.



                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00052   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2814                    Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      List of Subjects in 42 CFR Part 73                      Lassa fever virus                                      of any select agent viruses to a validated
                                                        Biologics, Packaging and containers,                  Lujo virus                                             sterility testing protocol to ensure that
                                                      Penalties, Reporting and recordkeeping                  Marburg virus*                                         the inactivation method has rendered
                                                      requirements, Transportation.                           Monkeypox virus                                        the select agent non-viable or regulated
                                                                                                              Reconstructed replication competent                    nucleic acids non-infectious.
                                                        For the reasons discussed in the                                                                                (D) Any viability of a select agent or
                                                                                                                 forms of the 1918 pandemic influenza
                                                      preamble, we propose to amend 42 CFR                                                                           infectivity of regulated nucleic acids
                                                                                                                 A virus containing any portion of the
                                                      part 73 as follows:                                                                                            that can produce infectious forms of any
                                                                                                                 coding regions of all eight gene
                                                      PART 73—SELECT AGENTS AND                                  segments (Reconstructed 1918                        select agent virus that was subjected to
                                                      TOXINS                                                     influenza A virus)                                  a validated inactivation protocol is
                                                                                                              Ricin                                                  reported to APHIS or CDC.
                                                      ■ 1. The authority citation for part 73                 SARS coronavirus (SARS-CoV)                               (E) Reviews annually, and revises as
                                                      continues to read as follows:                           Saxitoxin                                              necessary, the following:
                                                                                                              South American hemorrhagic fever                          (1) The kill curve procedure and
                                                        Authority: 42 U.S.C. 262a; sections 201–                                                                     results;
                                                      2014, 221 and 231 of Title II of Public Law                viruses:
                                                                                                              Chapare                                                   (2) Site-specific standard operating
                                                      107–188, 116 Stat 637 (42 U.S.C. 262a).
                                                                                                              Guanarito                                              procedures to ensure that select agents
                                                      ■ 2. Section 73.1 is amended by adding                                                                         or regulated nucleic acids that can
                                                      in alphabetical order, definitions of                   Junin
                                                                                                              Machupo                                                produce infectious forms of any select
                                                      inactivation and kill curve to read as set                                                                     agent virus are inactivated by a safety
                                                      forth below.                                            Sabia
                                                                                                              Staphylococcal enterotoxins (subtypes                  margin; and
                                                      § 73.1   Definitions.                                      A–E)                                                   (3) The validated sterility testing
                                                                                                              T–2 toxin                                              protocol used to ensure that the
                                                      *      *      *   *     *
                                                                                                              Tetrodotoxin                                           inactivation method has rendered a
                                                         Inactivation means a method to
                                                                                                              Tick-borne encephalitis virus                          select agent non-viable or regulated
                                                      render a select agent non-viable but
                                                                                                                 Far Eastern subtype                                 nucleic acids that can produce
                                                      retain characteristic of interest for future
                                                                                                                 Siberian subtype                                    infectious forms of any select agent
                                                      use, or to render any nucleic acids that
                                                                                                              Kyasanur Forest disease virus                          virus sample non-infectious.
                                                      can produce infectious forms of any                                                                               (F) Reviews, and revises as necessary,
                                                      select agent virus non-infectious for                   Omsk haemorrhagic fever virus
                                                                                                              Variola major virus (Smallpox virus) *                 documents listed in paragraph
                                                      future use.                                                                                                    (d)(2)(i)(E) of this section after any
                                                      *      *      *   *     *                               Variola minor virus (Alastrim) *
                                                                                                              Yersinia pestis*                                       change in principal investigator, change
                                                         Kill curve means the results of a dose-                                                                     in protocol, or any reported viability of
                                                      response experiment where a select                      *      *     *    *     *                              a select agent or infectivity of regulated
                                                      agent is subjected to increasing amounts                   (d)* * *                                            nucleic acids that can produce
                                                      of the inactivating treatment to                           (2) Non-viable HHS select agents or                 infectious forms of any select agent
                                                      determine the minimum conditions                        nonfunctional HHS toxins.                              viruses previously assessed as inactive.
                                                      required to render it non-viable or to                     (i) Unless waived by the HHS                           (ii) Unless waived by the HHS
                                                      render any nucleic acids that can                       Secretary, a select agent or regulated                 Secretary, an extract from a select agent
                                                      produce infectious forms of any select                  nucleic acids that can produce                         is not excluded from the requirements
                                                      agent virus as non-infectious.                          infectious forms of any select agent                   of this part until an individual or entity
                                                      *      *      *   *     *                               virus that has been subjected to a                     meets the following requirements:
                                                      ■ 3. Section 73.3 is amended as follows:                validated inactivation process to remove                  (A) Any extract is subjected to a
                                                      ■ a. By revising paragraph (b).                         viability or infectious form (i.e., the                process that removes all viable cells,
                                                      ■ b. By adding new paragraphs (d)(2)(i),                ability to reproduce or produce disease,               spores, or virus particles.
                                                      (ii), and (iii).                                        while maintaining cellular structure) is                  (B) Any extract is subjected to a
                                                      ■ c. By revising paragraphs (d)(3)                      not excluded from the requirements of                  validated sterility testing protocol to
                                                      introductory text and (d)(3)(i).                        this part until an individual or entity:               ensure that the inactivation method has
                                                      ■ d. By redesignating paragraph (d)(5) as                  (A) Develops a site-specific kill curve             rendered the extract free of a select
                                                      paragraph (d)(7).                                       to define conditions of inactivation for               agent.
                                                      ■ e. By adding new paragraphs (d)(5),                   each select agent or regulated nucleic                    (C) Any viability of an extract that
                                                      (d)(6), and (d)(8).                                     acids that can produce infectious forms                was subjected to a validated inactivation
                                                      ■ f. By adding paragraph (e)(3) to read                 of any select agent virus. If there are                protocol is reported to the Responsible
                                                      as set forth below.                                     strain-to-strain variations in resistance              Official.
                                                         The additions and revisions read as                  of a select agent to the inactivation                     (D) Any viability of a select agent or
                                                      follows:                                                procedure, then a specific kill curve                  infectivity of regulated nucleic acids
                                                                                                              must be developed for each strain that                 that can produce infectious forms of any
                                                      § 73.3   HHS select agents and toxins.                  undergoes the inactivation procedure. A                select agent virus that was previously
                                                      *     *    *     *     *                                new kill curve must be created upon                    assessed as inactive by their validated
                                                        (b) HHS select agents and toxins:                     any change in procedure or inactivation                sterility testing protocol is reported to
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      Abrin                                                   equipment.                                             APHIS or CDC.
                                                      Botulinum neurotoxins*                                     (B) Develops site-specific standard                    (3) Except as required in § 73.16(l),
                                                      Botulinum neurotoxin producing                          operating inactivation procedures to                   the aggregate amount of the toxin under
                                                        species of Clostridium*                               ensure that the material is inactivated                the control of a principal investigator,
                                                      Crimean-Congo hemorrhagic fever virus                   by a safety margin determined by the                   treating physician or veterinarian, or
                                                      Diacetoxyscirpenol                                      kill curve.                                            commercial manufacturer or distributor
                                                      Eastern equine encephalitis virus                          (C) Subjects representative samples of              does not, at any time, exceed the
                                                      Ebola virus*                                            inactivated select agents or any nucleic               following amounts: 1000 mg of Abrin; 1
                                                      Francisella tularensis*                                 acids that can produce infectious forms                mg of Botulinum neurotoxins; 10,000


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00053   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                            2815

                                                      mg of Diacetoxyscirpenol; 1000 mg of                    ■ c. By adding paragraph (d)(4).                       agent viruses are inactivated by a safety
                                                      Ricin; 500 mg of Saxitoxin; 100 mg of                   ■ d. By adding paragraph (e)(3).                       margin; and
                                                      Staphylococcal enterotoxins (subtypes                     The revision and additions read as                      (3) The validated sterility testing
                                                      A–E); 10,000 mg of T–2 toxin; or 500 mg                 follows:                                               protocol used to ensure that the
                                                      of Tetrodotoxin.                                                                                               inactivation method has rendered a
                                                                                                              § 73.4   Overlap select agents and toxins.
                                                         (i) The toxin is transferred only after                                                                     select agent non-viable or regulated
                                                      the transferor uses due diligence and                   *      *     *     *     *                             nucleic acids that can produce
                                                      documents the identification of the                        (b) Overlap select agents and toxins:               infectious forms of any select agent
                                                      recipient and the legitimate need (i.e.,                Bacillus anthracis*                                    viruses non-infectious.
                                                      prophylactic, protective, bona fide                     Burkholderia mallei*                                      (F) Reviews, and revises as necessary,
                                                      research, or other peaceful purpose)                    Burkholderia pseudomallei*                             documents listed in paragraph
                                                      claimed by the recipient to use such                    Hendra virus
                                                                                                                                                                     (d)(2)(i)(E) of this section after any
                                                                                                              Nipah virus
                                                      toxin. Information to be documented                                                                            change in principal investigator, change
                                                                                                              Rift Valley fever virus
                                                      includes, but is not limited to, the                                                                           in protocol, or any reported viability of
                                                                                                              Venezuelan equine encephalitis virus
                                                      recipient identity information,                                                                                a select agent or infectivity of regulated
                                                      including the recipient’s name,                         *      *     *     *     *                             nucleic acids that can produce
                                                      institution name, address, telephone                       (d) * * *                                           infectious forms of any select agent
                                                      number and email address; name of the                      (2) * * *
                                                                                                                                                                     virus previously assessed as inactive.
                                                                                                                 (i) Unless waived by the APHIS
                                                      toxin and the total amount transferred,                                                                           (ii) Unless waived by the APHIS
                                                                                                              Administrator or HHS Secretary, a select
                                                      and the legitimate need claimed by the                                                                         Administrator or HHS Secretary, an
                                                                                                              agent or regulated nucleic acids that can
                                                      recipient. Notwithstanding the                                                                                 extract from a select agent is not
                                                                                                              produce infectious forms of any select
                                                      provisions of paragraph (d) of this                                                                            excluded from the requirements of this
                                                                                                              agent virus that has been subjected to a
                                                      section, the HHS Secretary retains the                                                                         part until an individual or entity meets
                                                                                                              validated inactivation process to remove
                                                      authority to, without prior notification,                                                                      the following requirements:
                                                                                                              viability or infectious form (i.e., the
                                                      inspect and copy or request the                                                                                   (A) Any extract is subjected to a
                                                                                                              ability to reproduce or produce disease,
                                                      submission of the due diligence                                                                                process that removes all viable cells,
                                                                                                              while maintaining cellular structure) is
                                                      documentation to the CDC.                                                                                      spores, or virus particles.
                                                                                                              not excluded from the requirements of
                                                      *      *      *    *     *                                                                                        (B) Any extract is subjected to a
                                                                                                              this part until an individual or entity:
                                                         (5) An HHS select toxin identified in                   (A) Develops a site-specific kill curve             validated sterility testing protocol to
                                                      an original food sample or clinical                     to define conditions of inactivation for               ensure that the inactivation method has
                                                      sample.                                                 each select agent or regulated nucleic                 rendered the extract free of a select
                                                         (6) Select toxins that are produced as               acids that can produce infectious forms                agent.
                                                      a byproduct in the study of the toxin                   of any select agent viruses. If there are                 (C) Any viability of an extract that
                                                      producing host organism so long as the                  strain-to-strain variations in resistance              was subjected to a validated inactivation
                                                      toxin has not been intentionally                        of a select agent to the inactivation                  protocol is reported to the Responsible
                                                      cultivated, collected, purified, or                     procedure, then a specific kill curve                  Official.
                                                      otherwise extracted, and the material                   must be developed for each strain that                    (D) Any viability of a select agent or
                                                      containing the toxin is rendered non-                   undergoes the inactivation procedure. A                infectivity of regulated nucleic acids
                                                      functional and disposed of within 30                    new kill curve must be created upon                    that can produce infectious forms of any
                                                      days of the initiation of the culture.                  any change in procedure or inactivation                select agent virus that was previously
                                                      *      *      *    *     *                              equipment.                                             assessed as inactive by the validated
                                                         (8) Waste generated during the                          (B) Develops site-specific standard                 sterility testing protocol is reported to
                                                      delivery of patient care from a patient                 operating inactivation procedures to                   APHIS or CDC.
                                                      infected with a select agent that is                    ensure that the material is inactivated                   (d) * * *
                                                      decontaminated with a validated                         by a safety margin determined by the                      (4) Waste generated during the
                                                      method within seven calendar days of                    kill curve.                                            delivery of patient care from a patient
                                                      the conclusion of patient care,                            (C) Subjects representative samples of              infected with a select agent that is
                                                         (e) * * *                                            inactivated select agents or nucleic                   decontaminated with a validated
                                                         (3) An individual or entity may make                 acids that can produce infectious forms                method within seven calendar days of
                                                      a written request to the HHS Secretary                  of any select agent viruses to a validated             the conclusion of patient care.
                                                      for reconsideration of a decision                       sterility testing protocol to ensure that                 (e) * * *
                                                      denying an application for the exclusion                the inactivation method has rendered a                    (3) An individual or entity may make
                                                      of an attenuated strain of a select agent               select agent non-viable or regulated                   a written request to the HHS Secretary
                                                      or a select toxin modified to be less                   nucleic acids non-infectious.                          or APHIS Administrator for
                                                      potent or toxic. The written request for                   (D) Reports any viability of a select               reconsideration of a decision denying an
                                                      reconsideration must state the facts and                agent or infectivity of regulated nucleic              application for the exclusion of an
                                                      reasoning upon which the individual or                  acids that can produce infectious forms                attenuated strain of a select agent or a
                                                      entity relies to show the decision was                  of any select agent virus that was                     select toxin modified to be less potent
                                                      incorrect. The HHS Secretary will grant                 subjected to a validated inactivation                  or toxic. The written request for
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      or deny the request for reconsideration                 protocol to the Responsible Official.                  reconsideration must state the facts and
                                                      as promptly as circumstances allow and                     (E) Reviews annually, and revises as                reasoning upon which the individual or
                                                      will state, in writing, the reasons for the             necessary, the following:                              entity relies to show the decision was
                                                      decision.                                                  (1) The kill curve procedure and                    incorrect. The HHS Secretary or APHIS
                                                      *      *      *    *     *                              results;                                               Administrator will grant or deny the
                                                      ■ 4. Section 73.4 is amended as follows:                   (2) Site-specific standard operating                request for reconsideration as promptly
                                                      ■ a. By revising paragraph (b).                         procedures to ensure that select agents                as circumstances allow and will state, in
                                                      ■ b. By adding new paragraphs (d)(2)(i),                or regulated nucleic acids that can                    writing, the reasons for the decision.
                                                      (ii), and (iii).                                        produce infectious forms of any select                 *       *    *     *     *


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00054   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2816                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      ■ 5. Section 73.5 is amended as follows:                specimen provider, and to other                        ‘‘passwords’’ and removing ‘‘numbers’’
                                                      ■ a. By revising paragraph (a)(1).                      appropriate authorities when required                  and adding in its place ‘‘permissions’’.
                                                      ■ b. By redesignating paragraph (a)(3) as               by Federal, State, or local law by                     ■ b. By adding paragraph (c)(11).
                                                      paragraph (a)(4) and revising newly                     telephone, facsimile, or email. This                   ■ c. By adding paragraph (d)(7)(vi).
                                                      redesignated paragraph (a)(4).                          report must be followed by submission                  ■ d. By adding a sentence to the end of
                                                      ■ c. By adding new paragraph (a)(3).                    of APHIS/CDC Form 4 to APHIS or CDC                    paragraph (h).
                                                        The revisions and addition read as                    within 7 calendar days after                              The additions read as follows:
                                                      follows:                                                identification.                                        § 73.11   Security.
                                                      § 73.5 Exemptions for HHS select agents                 *     *     *    *      *                              *      *     *     *     *
                                                      and toxins.                                             ■ 7. Section 73.7 is amended as follows:
                                                                                                                                                                        (c) * * *
                                                                                                              ■ a. By redesignating paragraphs (b)
                                                         (a) * * *                                                                                                      (11) Describe how the entity
                                                         (1) Unless directed otherwise by the                 through (k) as paragraphs (c) through (l),
                                                                                                                                                                     authorizes the means of entry into areas
                                                      HHS Secretary, within seven calendar                    respectively.
                                                                                                              ■ b. By adding a new paragraph (b) to
                                                                                                                                                                     where select agents or toxins are stored
                                                      days after identification of the select                                                                        or used, to include centralized access
                                                                                                              read as follows:
                                                      agent and toxin (except for Botulinum                                                                          control management systems (e.g.,
                                                      neurotoxin and/or Staphylococcal                        § 73.7 Registration and related security               keycards) and/or mechanical key
                                                      enterotoxin (Subtypes A–E)), or within                  risk assessments.                                      management.
                                                      thirty calendar days after identification               *      *     *     *    *                                 (d) * * *
                                                      of Botulinum neurotoxin and/or                             (b) As a condition of registration, each               (7) * * *
                                                      Staphylococcal enterotoxin (Subtypes                    entity is required to be in compliance                    (vi) Any loss of computer, hard drive
                                                      A–E), the select agent or toxin is                      with the requirements of this part for                 or other data storage device containing
                                                      transferred in accordance with § 73.16                  select agents and toxins listed on the                 information that could be used to gain
                                                      or destroyed on-site by a recognized                    registration regardless of whether the                 access to select agents or toxins.
                                                      sterilization or inactivation process,                  entity is in actual possession of the                  *      *     *     *     *
                                                      *      *    *     *     *                               select agent or toxin. With regard to                     (h) * * * Drills or exercises must be
                                                         (3) Unless otherwise directed by the                 toxins, the entity registered for                      documented to include how the drill or
                                                      HHS Secretary, the clinical or diagnostic               possession, use or transfer of a toxin                 exercise tested and evaluated the plan,
                                                      specimens collected from a patient                      must be in compliance with the                         any problems that were identified and
                                                      infected with a select agent are                        requirements of this part regardless of                corrective action(s) taken, and all
                                                      transferred in accordance with § 73.16                  the amount of toxin currently in                       individuals who participated in the drill
                                                      or destroyed on-site by a recognized                    possession.                                            or exercise.
                                                      sterilization or inactivation process                   *      *     *     *    *                              ■ 11. Section 73.12 is amended as
                                                      within seven days after delivery of                     ■ 8. Section 73.9 is amended as follows:               follows:
                                                      patient care has concluded, and                         ■ a. In paragraph (a)(6) by removing                   ■ a. By revising paragraph (a).
                                                         (4) The identification of the agent or               ‘‘laboratory’’ and adding in its place                 ■ b. By removing paragraph (c)(2),
                                                      toxin is reported to CDC or APHIS, the                  ‘‘registered space’’ and adding ‘‘and the              redesignating paragraph (c)(3) as (c)(2),
                                                      specimen provider, and to other                         corrections documented’’ after                         and in newly redesignated paragraph
                                                      appropriate authorities when required                   ‘‘corrected’’ at the end of the sentence.              (c)(2), removing ‘‘NIH Guidelines for
                                                      by Federal, State, or local law by                      ■ b. By adding paragraph (a)(7) to read                Research Involving Recombinant DNA
                                                      telephone, facsimile, or email. This                    as set forth below.                                    Molecules’’ and adding in its place
                                                      report must be followed by submission                                                                          ‘‘NIH Guidelines for Research Involving
                                                      of APHIS/CDC Form 4 to APHIS or CDC                     § 73.9   Responsible Official.                         Recombinant or Synthetic Nucleic Acid
                                                      within 7 calendar days after                               (a) * * *                                           Molecules’’.
                                                      identification.                                            (7) Ensure that individuals are                     ■ c. By adding a new sentence to the
                                                      *      *    *     *     *                               provided the contact information for the               end of paragraph (e).
                                                      ■ 6. Section 73.6 is amended as follows:
                                                                                                              HHS or USDA Office of Inspector                           The revision and addition read as
                                                      ■ a. By redesignating paragraph (a)(3) as
                                                                                                              General Hotline so that they may                       follows:
                                                      paragraph (a)(4) and revising newly                     anonymously report any safety or
                                                                                                              security concerns related to select                    § 73.12   Biosafety.
                                                      redesignated paragraph (a)(4).
                                                                                                              agents and toxins.                                       (a) An individual or entity required to
                                                      ■ b. By adding paragraph (a)(3).
                                                         The revision and addition read as                    *      *     *     *    *                              register under this part must develop
                                                      follows:                                                ■ 9. Section 73.10 is amended by adding                and implement a written biosafety plan
                                                                                                              a new sentence to the end of paragraph                 that is commensurate with the risk of
                                                      § 73.6 Exemptions for overlap select                    (e) to read as follows:                                the select agent or toxin, given its
                                                      agents and toxins.                                                                                             intended use. The biosafety plan must
                                                         (a) * * *                                            § 73.10 Restricting access to select agents            contain sufficient information and
                                                         (3) Unless otherwise directed by the                 and toxins; security risk assessments.                 documentation to describe the biosafety
                                                      HHS Secretary or Administrator, the                     *      *     *    *     *                              and containment procedures for the
                                                      clinical or diagnostic specimens                           (e) * * * A Responsible Official must               select agent or toxin, including any
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      collected from a patient infected with a                immediately notify the Responsible                     animals (including arthropods) or plants
                                                      select agent are transferred in                         Official of the visited entity if the                  intentionally or accidentally exposed to
                                                      accordance with § 73.16 or destroyed                    person’s access to select agents and                   or infected with a select agent. Biosafety
                                                      on-site by a recognized sterilization or                toxins has been terminated.                            and containment procedures specific to
                                                      inactivation process within seven days                  *      *     *    *     *                              each registered laboratory must be
                                                      after delivery of patient care has                      ■ 10. Section 73.11 is amended as                      available to each individual working in
                                                      concluded, and                                          follows:                                               that laboratory. The current biosafety
                                                         (4) The identification of the agent or               ■ a. In paragraph (c)(5) by adding                     plan must be submitted for initial
                                                      toxin is reported to CDC or APHIS, the                  ‘‘keycards,’’ between ‘‘keys,’’ and                    registration, renewal of registration, or


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00055   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                                             Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules                                               2817

                                                      when requested. The biosafety plan                      any problems that were identified and                  ■  15. Section 73.17 is amended as
                                                      must include the following provisions:                  corrective action(s) taken, and all                    follows:
                                                         (1) A written risk assessment for each               individuals who participated in the drill              ■ a. In paragraphs (a)(1)(iii) and (a)(3)(v)
                                                      procedure involving a select agent or                   or exercise.                                           by adding ‘‘or other storage container’’
                                                      toxin that addresses the hazards                        ■ 12. Section 73.14 is amended as                      after ‘‘freezer’’.
                                                      associated with the agent or toxin.                     follows:                                               ■ b. By adding paragraph (a)(1)(ix).
                                                         (i) The hazardous characteristics of                 ■ a. By adding a new sentence to the                   ■ c. By adding paragraph (a)(8).
                                                      each agent or toxin listed on the entity’s              end of paragraph (a).                                  ■ d . In paragraph (b) by adding
                                                      registration, including probable routes                 ■ b. By adding a new sentence to the                   ‘‘legible,’’ after ‘‘are’’.
                                                      of transmission in the laboratory and in                end of paragraph (f).                                  ■ e. By revising paragraph (c).
                                                      the environment, infective dose (if                       The additions read as follows:                          The revision and additions read as
                                                      known), stability in the environment,                   § 73.14    Incident response.
                                                                                                                                                                     follows:
                                                      host range, contribution of any genetic
                                                      manipulations, and endemicity.                             (a) * * * The current incident                      § 73.17   Records.
                                                         (ii) Hazards associated with laboratory              response plan must be submitted for                       (a) * * *
                                                      procedures related to the select agent or               initial registration, renewal of                          (1) * * *
                                                      toxin;                                                  registration, or when requested.                          (ix) If destroyed, the quantity (e.g.,
                                                         (2) Safeguards in place with                         *      *     *      *     *                            containers, vials, tubes, etc.) of select
                                                      associated work practices to protect                       (f) * * * Drills or exercises must be               agent destroyed, the date of such action,
                                                      registered entity personnel, the public,                documented to include how the drill or                 and by whom.
                                                      and the environment from exposure to                    exercise tested and evaluated the plan,                *       *    *      *     *
                                                      the select agent or toxin including, but                any problems that were identified and                     (8) For a select agent or an extract
                                                      not limited to: Safety training                         corrective action(s) taken, and all                    from a select agent that has been
                                                      requirements for registered entity                      individuals who participated in the drill              rendered non-viable or regulated
                                                      personnel performing the procedure;                     or exercise.                                           nucleic acids that can produce
                                                      required personal protective equipment                  ■ 13. Section 73.15 is amended as                      infectious forms of any select agent
                                                      and other safety equipment; required                    follows:                                               virus that have been rendered non-
                                                                                                              ■ a. In paragraph (a)(1) by removing
                                                      containment equipment including, but                                                                           infectious through inactivation:
                                                      not limited to, biological safety cabinets,             ‘‘before that individual has such access                  (i) A written description of the
                                                      animal caging systems, and centrifuge                   to select agents and toxins’’ and adding               inactivation process used for rendering
                                                      safety containers; and required                         in its place ‘‘, within 12 months of that              a select agent non-viable or regulated
                                                      engineering controls and other facility                 individual’s anniversary of receiving                  nucleic acids that can produce
                                                      safeguards.                                             such approval or prior to his or her                   infectious forms of any select agent
                                                         (3) Written procedures for                           entry into an area where select agents or              virus non-infectious;
                                                      decontamination with a validated                        toxins are used or stored, whichever                      (ii) The sterility testing protocol used
                                                      method, of all contaminated or                          occurs first.’’.                                       to verify non-viability of a select agent
                                                                                                              ■ b. By adding paragraph (e) to read as
                                                      potentially contaminated materials                                                                             or non-infectivity of regulated nucleic
                                                      including, but not limited to: Cultures                 set forth below.                                       acids that can produce infectious forms
                                                      and other materials related to the                      § 73.15    Training.                                   of any select agent virus and the results
                                                      propagation of select agents or toxins,                 *     *    *     *      *                              of the test, including investigation, of
                                                      items related to the analysis of select                   (e) The Responsible Official must                    any inactivation process failures and the
                                                      agents and toxins, personal protective                  ensure and document that individuals                   corrective actions taken;
                                                      equipment, animal caging systems and                    are provided the contact information of                   (iii) The name of each individual
                                                      bedding, and animal carcasses or                        the HHS or USDA Office of Inspector                    performing the inactivation method and
                                                      extracted tissues.                                      General Hotline so that they may                       sterility testing protocols;
                                                         (4) Written procedures for                           anonymously report any safety or                          (iv) The date(s) the inactivation
                                                      decontamination, with a validated                       security concerns related to select                    method and sterility testing protocols
                                                      method, of laboratory surfaces and                      agents and toxins.                                     were completed;
                                                      equipment using manufacturer’s                          ■ 14. Section 73.16 is amended by                         (v) The location where the inactivated
                                                      specification.                                          revising paragraph (l)(1) to read as                   method and sterility testing protocols
                                                         (5) Effluent decontamination                         follows:                                               were performed; and
                                                      procedures, with a validated method,                                                                              (vi) An inactivation certificate that
                                                      that describe the treatment of effluent                 § 73.16    Transfers.                                  includes the date of inactivation,
                                                      material contaminated with select                       *      *     *    *     *                              method of inactivation, date of final
                                                      agents and toxins.                                         (l) * * *                                           sterility testing protocol result, and the
                                                         (6) Procedures to respond to                            (1) Transfer the amounts only after the             Principal Investigator. A copy of the
                                                      emergencies such as spills, sharps                      transferor uses due diligence and                      inactivation certificate must accompany
                                                      injury, or animal bites involving select                documents that the recipient has a                     any transfer of inactivated material.
                                                      agents and toxins.                                      legitimate need (i.e., prophylactic,                   *       *    *      *     *
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                         (7) Procedures for the handling of                   protective, bona fide research, or other                  (c) Any records that contain
                                                      select agents and toxins in the same                    peaceful purpose) to handle or use such                information related to the requirements
                                                      spaces with non-select agents and toxins                toxins. Information to be documented                   of the regulations. Such records may
                                                      in order to prevent unintentional                       includes, but is not limited, to the                   include, but are not limited to,
                                                      contamination.                                          recipient information, toxin and amount                biocontainment certifications,
                                                      *       *    *     *     *                              transferred, and declaration that the                  laboratory notebooks, institutional
                                                         (e) * * * Drills or exercises must be                recipient has legitimate purpose to store              biosafety and/or animal use committee
                                                      documented to include how the drill or                  and use such toxins.                                   minutes and approved protocols, and
                                                      exercise tested and evaluated the plan,                 *      *     *    *     *                              records associated with occupational


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00056   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1


                                                      2818                   Federal Register / Vol. 81, No. 11 / Tuesday, January 19, 2016 / Proposed Rules

                                                      health and suitability programs. All                    mailing address, and MB Docket No.                     it might ‘‘further reduce the information
                                                      records created under this part must be                 13–249.                                                collection burden for small business
                                                      maintained for 3 years.                                    • Paper Filers: Parties who choose to               concerns with fewer than 25
                                                      *    *     *     *     *                                file by paper must file an original and                employees.’’
                                                                                                              one copy of each filing. Filings can be                   In addition to filing comments with
                                                        Dated: January 12, 2016.
                                                                                                              sent by hand or messenger delivery, by                 the Secretary, a copy of any Paperwork
                                                      Sylvia M. Burwell,                                      commercial overnight courier, or by                    Reduction Act comments on the
                                                      Secretary.                                              first-class or overnight U.S. Postal                   information collection requirements
                                                      [FR Doc. 2016–00758 Filed 1–14–16; 4:15 pm]             Service mail (although the Commission                  contained herein should be submitted to
                                                      BILLING CODE 4163–18–P                                  continues to experience delays in                      Cathy Williams, Federal
                                                                                                              receiving U.S. Postal Service mail). All               Communications Commission, Room 1–
                                                                                                              filings must be addressed to the                       C823, 445 12th Street SW., Washington,
                                                      FEDERAL COMMUNICATIONS                                  Commission’s Secretary, Office of the                  DC 20554, or via the Internet to
                                                      COMMISSION                                              Secretary, Federal Communications                      Cathy.Williams@fcc.gov, and to
                                                                                                              Commission.                                            Nicholas A. Fraser, Office of
                                                      47 CFR Parts 73 and 74                                  For detailed instructions for submitting               Management and Budget (OMB), via the
                                                      [MB Docket No. 13–249; FCC 15–142]                      comments and additional information                    Internet to Nicholas_A._Fraser@
                                                                                                              on the rulemaking process, see the                     omb.eop.gov.
                                                      Revitalization of the AM Radio Service                  SUPPLEMENTARY INFORMATION section of                      To view a copy of this information
                                                                                                              this document.                                         collection request (ICR) submitted to
                                                      AGENCY:  Federal Communications                         FOR FURTHER INFORMATION CONTACT:                       OMB: (1) Go to the Web page http://
                                                      Commission.                                             Peter Doyle, Chief, Media Bureau,                      www.reginfo.gov/public/do/PRAMain,
                                                      ACTION: Proposed rule.                                  Audio Division, (202) 418–2700;                        (2) look for the section of the Web page
                                                                                                              Thomas Nessinger, Senior Counsel,                      called ‘‘Currently Under Review,’’ (3)
                                                      SUMMARY:    In this document, the                       Media Bureau, Audio Division, (202)                    click on the downward-pointing arrow
                                                      Commission adopted a Further Notice of                  418–2700. For additional information                   in the ‘‘Select Agency’’ box below the
                                                      Proposed Rulemaking (FNPRM), in                         concerning the Paperwork Reduction                     ‘‘Currently Under Review’’ heading, (4)
                                                      which it sought comment on several                      Act (PRA) information collection                       select ‘‘Federal Communications
                                                      proposals designed to revitalize the AM                 requirements contained in this                         Commission’’ from the list of agencies
                                                      broadcast radio service, or to reduce                   document, contact Cathy Williams at                    presented in the ‘‘Select Agency’’ box,
                                                      burdens on AM broadcasters. The                         202–418–2918, or via the Internet at                   (5) click the ‘‘Submit’’ button to the
                                                      Commission further adopted a Notice of                  Cathy.Williams@fcc.gov.                                right of the ‘‘Select Agency’’ box, (6)
                                                      Inquiry (NOI), in which it sought                                                                              when the list of FCC ICRs currently
                                                                                                              SUPPLEMENTARY INFORMATION: This is a
                                                      comment on two proposals designed to                                                                           under review appears, look for the Title
                                                      revitalize the AM broadcast radio                       summary of the Commission’s Further
                                                                                                              Notice of Proposed Rulemaking, FCC                     of this ICR and then click on the ICR
                                                      service. One of the proposals, regarding                                                                       Reference Number. A copy of the FCC
                                                      increased utilization of the AM                         15–142, adopted October 21, 2015, and
                                                                                                              released October 23, 2015.                             submission to OMB will be displayed.
                                                      expanded band, was suggested by
                                                                                                                                                                        The proposed information collections
                                                      several commenters in response to the                   Initial Paperwork Reduction Act of                     are as follows:
                                                      NPRM in this proceeding, The second                     1995 Analysis
                                                      proposal, for relaxation of the                                                                                   OMB Control Number: 3060–0075.
                                                                                                                The FNPRM contains proposed                             Title: Application for Transfer of
                                                      Commission’s main studio rules for AM
                                                                                                              information collection requirements                    Control of a Corporate Licensee or
                                                      stations, was suggested by a commenter
                                                                                                              subject to the PRA, Public Law 104–13.                 Permittee, or Assignment of License or
                                                      and supported by others.
                                                                                                              OMB, the general public, and other                     Permit, for an FM or TV Translator
                                                      DATES: Comments may be filed on or                      Federal agencies are invited to comment                Station, or a Low Power Television
                                                      before March 21, 2016 and reply                         on the proposed new and modified                       Station, FCC Form 345.
                                                      comments may be filed on or before                      information collection requirements
                                                      April 18, 2016. Written comments on                                                                               Type of Review: Revision of a
                                                                                                              contained in this FNPRM.                               currently approved collection.
                                                      the Paperwork Reduction Act proposed                      Comments on the proposed
                                                      information collection requirements                                                                               Respondents: Business or other for-
                                                                                                              information collection requirements
                                                      must be submitted by the public, Office                                                                        profit entities; Not for profit institutions;
                                                                                                              should address: (a) Whether the
                                                      of Management and Budget (OMB), and                                                                            Local or Tribal Government.
                                                                                                              proposed collection of information is
                                                      other interested parties on or before                                                                             Number of Respondents and
                                                                                                              necessary for the proper performance of
                                                      March 21, 2016.                                                                                                Responses: 1,700 respondents; 2,700
                                                                                                              the functions of the Commission,
                                                                                                                                                                     responses.
                                                      ADDRESSES: You may submit comments,                     including whether the information shall
                                                      identified by MB Docket No. 13–249, by                  have practical utility; (b) the accuracy of               Estimated Time per Response: 0.084–
                                                      any of the following methods:                           the Commission’s burden estimates; (c)                 1.25 hours.
                                                         • Electronic Filers: Comments may be                 ways to enhance the quality, utility, and                 Frequency of Response: Third party
                                                      filed electronically using the Internet by              clarity of the information collected; and              disclosure requirement and on occasion
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS




                                                      accessing the Commission’s Electronic                   (d) ways to minimize the burden of the                 reporting requirement.
                                                      Comment Filing System (ECFS), through                   collection of information on the                          Total Annual Burden: 2,667 hours.
                                                      the Commission’s Web site http://                       respondents, including the use of                         Total Annual Cost: $3,958,125.
                                                      fjallfoss.fcc.gov/ecfs2/. Filers should                 automated collection techniques or                        Obligation to Respond: Required to
                                                      follow the instructions provided on the                 other forms of information technology.                 obtain or retain benefits. The statutory
                                                      Web site for submitting comments. For                   Pursuant to the Small Business                         authority for this collection of
                                                      ECFS filers, in completing the                          Paperwork Relief Act of 2002, Public                   information is contained in Sections
                                                      transmittal screen, filers should include               Law 107–198, see 44 U.S.C. 3506(c)(4),                 154(i) and 310 of the Communications
                                                      their full name, U.S. Postal service                    the FCC seeks specific comment on how                  Act of 1934, as amended.


                                                 VerDate Sep<11>2014   15:55 Jan 15, 2016   Jkt 238001   PO 00000   Frm 00057   Fmt 4702   Sfmt 4702   E:\FR\FM\19JAP1.SGM   19JAP1



Document Created: 2016-01-16 01:12:04
Document Modified: 2016-01-16 01:12:04
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionProposed Rules
ActionNotice of Proposed Rulemaking (NPRM).
DatesSubmit written or electronic comments by March 21, 2016.
ContactDr. Dan Sosin, Acting Director, Division of Select Agents and Toxins, Centers for Disease Control and Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, Georgia 30329. Telephone: (404) 718-2000.
FR Citation81 FR 2805 
RIN Number0920-AA59
CFR AssociatedBiologics; Packaging and Containers; Penalties; Reporting and Recordkeeping Requirements and Transportation

2025 Federal Register | Disclaimer | Privacy Policy
USC | CFR | eCFR